ORCID Profile
0000-0002-1471-7358
Current Organisation
Guangzhou First People’s Hospital, School of Medicine, South China University of Technology
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Related Links
Publications
Associations between serum IL-8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis.
Publisher: Springer Science and Business Media LLC
Date: 03-08-2019
DOI: 10.1007/S10067-019-04718-8
Abstract: The aim of this study was to investigate cross-sectional associations between serum levels of IL-8 and the above outcomes in patients with knee osteoarthritis (OA). A total of 160 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and Lequesne index were used to assess the joint symptom. Magnetic resonance imaging was used to measure knee structural abnormalities including infrapatellar fat pad (IPFP) signal intensity alternation. Knee radiographic OA was assessed by radiography using the Kellgren-Lawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of IL-8 and cartilage or bone biomarkers. In multivariable analyses, serum IL-8 was positively associated with WOMAC weight-bearing pain (β 2.85, P = 0.028), WOMAC physical dysfunction (β 12.71, P = 0.048), and Lequesne index (β 1.65, P = 0.015), and had positive associations with IPFP signal intensity alteration (OR 3.18, P = 0.011) and serum levels of N-telopeptide of type I collagen (NTXI), N-terminal procollagen III propeptide (PIIINP), matrix metalloproteinase (MMP)3, and MMP13 (β 0.24-1.44, all P < 0.05) in patients with clinical knee OA. Furthermore, there were positive associations between IL-8 and WOMAC score (β 22.49, P = 0.037), K-L grades (OR 3.88, P = 0.013), and IPFP signal intensity alteration (OR 3.20, P = 0.033) in patients with radiographic OA. Serum levels of IL-8 were positively associated with increased knee symptoms, IPFP signal intensity alteration, and serum levels of bone and/or cartilage biomarkers, suggesting that IL-8 may have a role to play in knee OA.Key Point• This study systemically investigates the associations between serum IL 8 and knee symptoms, joint structures, and cartilage or bone biomarkers in patients with knee osteoarthritis, and some significant associations have been found, suggesting that IL 8 may have a role to play in knee OA.
Signal intensity alteration and maximal area of pericruciate fat pad are associated with incident radiographic osteoarthritis: data from the Osteoarthritis Initiative
Publisher: Springer Science and Business Media LLC
Date: 29-07-2021
DOI: 10.1007/S00330-021-08193-1
Abstract: To determine whether pericruciate fat pad (PCFP) signal intensity alteration and maximal area are associated with incident radiographic osteoarthritis (ROA) over 4 years in the Osteoarthritis Initiative (OAI) study. Participants were from the Osteoarthritis Initiative (OAI) study. Case knees (n = 355) were defined by incident ROA between 12 and 48 months visits and were matched by sex, age, and radiographic status with control knees (n = 355). Magnetic resonance images (MRIs) were used to assess PCFP signal intensity alteration and PCFP maximal area at P0 (time of onset of ROA), P-1 (1 year prior to P0), and baseline. Conditional logistic regression analyses were applied to assess associations between PCFP measures and the risk of incident ROA. The mean age of participants was 60.1 years and 66.9% were women. In multivariable analyses, PCFP signal intensity alteration measured at three time points (OR [95%CI]: 1.28 [1.10-1.50], 1.52 [1.30-1.78], 1.50 [1.27-1.76], respectively) and PCFP maximal area (OR [95%CI]: 1.21 [1.03-1.42], 1.27 [1.07-1.52], 1.37 [1.15-1.62], respectively) were significantly associated with incident ROA. PCFP signal intensity alteration and maximal area were associated with incident ROA over 4 years, implying that they may have roles to play in ROA. • Pericruciate fat pad signal intensity alteration and maximal area were associated with incident ROA, implying that they may have roles to play in ROA.
Investigational drugs for the treatment of osteoarthritis, an update on recent developments
Publisher: Informa UK Limited
Date: 24-10-2018
DOI: 10.1080/13543784.2018.1539075
Abstract: Osteoarthritis (OA) is the leading cause of pain, loss of function, and disability among elderly, with the knee the most affected joint. It is a heterogeneous condition characterized by complex and multifactorial etiologies which contribute to the broad variation in symptoms presentation and treatment responses that OA patients present. This poses a challenge for the development of effective treatment on OA. This review will discuss recent development of agents for the treatment of OA, updating our previous narrative review published in 2015. They include drugs for controlling local and systemic inflammation, regulating articular cartilage, targeting subchondral bone, and relieving pain. Although new OA drugs such as monoclonal antibodies have shown marked effects and favorable tolerance, current treatment options for OA remain limited. The authors believe there is no miracle drug that can be used for all OA patients' treatment and disease stage is crucial for the effectiveness of drugs. Therefore, early diagnosis, phenotyping OA patients and precise therapy would expedite the development of investigational drugs targeting at symptoms and disease progression of OA.
Efficacy and safety of GLucocorticoid injections into InfrapaTellar faT pad in patients with knee ostEoarthRitiS: protocol for the GLITTERS randomized controlled trial
Publisher: Research Square Platform LLC
Date: 20-09-2022
DOI: 10.21203/RS.3.RS-2022263/V1
Abstract: Background Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and in idualized treatment targeting on inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown the repeated intra-articular glucocorticoid injections for a long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. Methods GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP at baseline, and be followed 4, 8, and 12 weeks. Primary outcomes will be changes in knee pain on a visual analogue scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). Secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher’s exact test). Discussion GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk-benefit profile of this treatment in the future. Trial registration ClinicalTrials. gov NCT05291650. Registered on 23/03/2022.
Metformin attenuates osteoarthritis by targeting chondrocytes, synovial macrophages and adipocytes
Publisher: Oxford University Press (OUP)
Date: 19-08-2022
DOI: 10.1093/RHEUMATOLOGY/KEAC467
Abstract: To investigate the therapeutic effect and mechanism of metformin on knee OA in normal diet (ND) mice or high-fat diet (HFD)-induced obese mice. Destabilization of the medial meniscus surgery was performed in ND mice or HFD mice, and metformin was administrated in drinking water or not. The changes of OA joint structure, infiltration and polarization of synovial macrophages and circulating and local levels of leptin and adiponectin were evaluated. In vitro, the effects of metformin on chondrocytes and macrophages, and of conditioned mediums derived from mouse abdominal fat on murine chondrogenic cell line ATDC5 and murine macrophage cell line RAW264.7, were detected. Metformin showed protective effects on OA, characterized by reductions on OARSI score [2.00, 95% CI (1.15, 2.86) for ND mice and 3.17, 95% CI (2.37, 3.96) for HFD mice] and synovitis score [1.17, 95% CI (0.27, 2.06) for ND mice and 2.50, 95% CI (1.49, 3.51) for HFD mice] after 10 weeks of treatment, and the effects were more significant in HFD mice than in ND mice. Mechanistically, in addition to decreasing apoptosis and matrix-degrading enzymes expression in chondrocytes as well as infiltration and pro-inflammatory differentiation of synovial macrophages, metformin reduced leptin secretion by adipose tissue in HFD mice. Metformin protects against knee OA which could be through reducing apoptosis and catabolism of chondrocytes, and suppressing infiltration and pro-inflammatory polarization of synovial macrophages. For obese mice, metformin has a greater protective effect in knee OA additionally through reducing leptin secretion from adipose tissue.
Evaluating the impact of metformin targets on the risk of osteoarthritis: a mendelian randomization study
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.JOCA.2022.06.010
Abstract: To provide some causal evidence concerning the effects of metformin on osteoarthritis (OA) using two metformin targets, namely AMP-activated protein kinase (AMPK) and growth differentiation factor 15 (GDF-15) as metformin proxies. This is a 2-s le Mendelian randomization design. We constructed 44 AMPK-related variants genetically predicted in HbA1c (%) as instruments for AMPK and five variants strongly predicted GDF-15 as instruments for GDF-15. Summary-level data for three OA phenotypes, including OA at any site, knee OA, and hip OA were obtained from the largest genome-wide meta-analysis across the UK Biobank and arcOGEN with 455,211 Europeans. Main analyses were conducted using the inverse-variance weighted method. Weighted median and MR-Egger were conducted as sensitivity analyses to assess the robustness of our results. Genetically predicted AMPK were negatively associated with OA at any site (OR: 0.60 95% CI: 0.43-0.83) and hip OA (OR: 0.42 95% CI: 0.22-0.80), but with not knee OA (OR: 0.85 95% CI: 0.49-1.50). Higher levels of genetically predicted GDF-15 reduced the risk of hip OA (OR: 0.95 95% CI: 0.90-0.99), but not OA at any site (OR: 1.00 95% CI: 0.98-1.02) and knee OA (OR: 1.02 95% CI: 0.98-1.07). This study indicates that AMPK and GDF-15 can be potential therapeutic targets for OA, especially for hip OA, and metformin would be repurposed for OA therapy which needs to be verified in randomized controlled trials.
Associations of Dietary Macroelements with Knee Joint Structures, Symptoms, Quality of Life, and Comorbid Conditions in People with Symptomatic Knee Osteoarthritis
Publisher: MDPI AG
Date: 30-08-2022
DOI: 10.3390/NU14173576
Abstract: Background: Osteoarthritis (OA), the most common joint disease in the elderly, has no cure. Macroelements are vital in human health and their relationships with OA are not clear. Clarifying the relationships between macroelements and OA may assist knee OA management. Methods: This study was a post-hoc analysis using data from a two-year randomized controlled trial among 392 participants with knee OA. Dietary macroelements, including calcium, magnesium, potassium, and phosphorus were computed-based on a semi-quantitative food frequency questionnaire at baseline. Knee joint structures (including cartilage volume, cartilage defect, bone marrow lesions, and effusion-synovitis volume), OA symptoms, quality of life, and OA comorbid conditions (including lower limb muscle strength and depressive symptoms) were assessed at baseline and month 24. Western Ontario and McMaster Universities (WOMAC) Index and depressive symptoms were assessed at baseline and months 3, 6, 12, and 24. Quality of life and lower limb muscle strength were assessed at baseline and months 6, 12, and 24. All analyses were conducted using mixed-effects models. Results: Higher dietary magnesium and potassium were associated with fewer OA symptoms, higher quality of life, greater lower limb muscle strength, and fewer depressive symptoms, but not with knee joint structures. Higher dietary calcium and phosphorus was not associated with any of the OA-related outcomes, except that dietary phosphorus was associated with greater lower limb muscle strength. Conclusions: In the longitudinal analyses, higher dietary magnesium and potassium intake are associated with fewer OA symptoms, higher quality of life, and milder comorbid conditions in patients with knee OA, suggesting dietary magnesium and potassium may have beneficial effects on OA and could be used for knee OA management.
Association of serum levels of inflammatory markers and adipokines with joint symptoms and structures in participants with knee osteoarthritis
Publisher: Oxford University Press (OUP)
Date: 11-06-2021
DOI: 10.1093/RHEUMATOLOGY/KEAB479
Abstract: To investigate the longitudinal associations of serum inflammatory markers and adipokines with joint symptoms and structures in participants with knee OA. Two hundred participants (46.5% female, mean age 63.1 years, mean BMI 29.5 kg/m2) from Tasmania, part of the VIDEO (Vitamin D Effect on OA) study, were randomly selected in the current study. Serum levels of 19 biomarkers, scores of WOMAC and MRI-assessed knee structures were evaluated at baseline and month 24. The patterns of biomarkers were derived from principal component analysis and their association with knee symptoms and structures were examined using adjusted generalized estimating equations. Five components explained 78% of the total variance. IL-1β, -2, -4, -6, -8, -17 A, -17 F, -21, -22 and -23 loaded the highest on the first component, which was associated with increased bone marrow lesions (BMLs) and WOMAC dysfunction score. IL-10, -12 and GM-CSF loaded on the second component, which was associated with increased cartilage volume, and decreased effusion synovitis and WOMAC scores. Leptin, adipsin and CRP loaded on the third component, which was positively associated with WOMAC scores. Resistin loaded on the fourth component, which was associated with increased BMLs and cartilage defects. Apelin-36 and adiponectin loaded on the fifth component, which was associated with increased BMLs. Various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting a complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA.
The effect of systemic iron status on osteoarthritis: A mendelian randomization study
Publisher: Frontiers Media SA
Date: 16-03-2023
DOI: 10.3389/FGENE.2023.1122955
Abstract: Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron transferrin saturation ferritin total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-s le Mendelian randomization (MR) design. Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associated with all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 in iduals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches. Results: Based on liberal instruments, genetically predicted serum iron and transferrin saturation were significantly associated with hip OA and total hip replacement, but not with knee OA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80). Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor.
Shedding light on experimental intra-articular drugs for treating knee osteoarthritis
Publisher: Informa UK Limited
Date: 03-06-2023
Associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee osteoarthritis
Publisher: Oxford University Press (OUP)
Date: 05-02-2021
DOI: 10.1093/RHEUMATOLOGY/KEAB092
Abstract: To describe the associations of blood pressure and arterial stiffness with knee cartilage volume in patients with knee OA. A secondary analysis was performed on the data from participants in a randomized controlled trial that identified the effects of vitamin D supplementation on knee structures and symptoms among patients with symptomatic knee OA. Brachial and central blood pressure, arterial stiffness indicators and knee cartilage volume were measured at baseline and the 2 year follow-up. Associations were assessed using generalized estimating equations. Among 231 participants (average age 63.2 years), 48.9% were females. Higher supine systolic and diastolic pressures were significantly associated with lower tibial cartilage volume (systolic: lateral β -6.23, medial β -5.14, total β -11.35 mm3/mmHg diastolic: lateral β -10.25, medial β -11.29, total β -21.50 mm3/mmHg). Higher supine systolic pressure was associated with lower femoral cartilage volume (lateral β -17.35, total β -28.31 mm3/mmHg). Central systolic pressure and arterial stiffness indicators (including pulse wave velocity, central pulse pressure and peripheral pulse pressure) were largely not associated with knee cartilage volume however, higher augmentation index was associated with lower tibial and femoral cartilage volume (tibial: medial β -8.24, total β -19.13 mm3/% femoral: lateral β -23.70, medial β -26.42, total β -50.12 mm3/%). Blood pressure and arterial stiffness are associated with knee cartilage volume at several sites in knee OA patients. This supports that blood pressure and arterial stiffness may involve in the progression of knee OA.
Associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage enzymes in patients with knee osteoarthritis
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JOCA.2018.08.020
Abstract: Animal studies suggest that S100A8/S100A9 may be involved in the pathogenesis of osteoarthritis (OA) however, there has been no clinical study examining the associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage degradation enzymes in knee OA patients so far. Therefore, this study was designed to investigate the cross-sectional associations between serum levels of S100A8/S100A9 and the outcomes in patients with knee OA. A total of 141 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess joint symptoms. Magnetic resonance imaging (MRI) was used to measure knee structural abnormalities including cartilage defects. Knee radiography was used to assess joint space narrowing (JSN), osteophytes and the radiographic severity of OA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of S100A8/S100A9, matrix metalloproteinase (MMP)-3, MMP10 and MMP13. In multivariable analyses, serum S100A8/S100A9 were positively associated with total WOMAC score (β: 0.111 per 10 ng/ml, P = 0.021), WOMAC weight-bearing pain (β: 0.015 per 10 ng/ml, P = 0.043) and WOMAC physical dysfunction (β: 0.091 per 10 ng/ml, P = 0.010), and had positive associations with total cartilage defects and cartilage defects at lateral femoral, lateral tibial and medial femoral sites (ORs: 1.006-1.008 per 10 ng/ml, all P < 0.05) and serum levels of MMP3 (β: 0.002 per 10 ng/ml, P = 0.032) in patients with clinical knee OA. Serum levels of S100A8/S100A9 were positively associated with increased knee symptoms, cartilage defects and serum cartilage degradation enzymes in patients with knee OA, suggesting that S100A8/S100A9 may have a role to play in knee OA. Future longitudinal studies are required to confirm these findings.
Evaluating the causal effect of circulating proteome on the risk of osteoarthritis-related traits
Publisher: BMJ
Date: 18-08-2023
Abstract: This study aims to identify circulating proteins that are causally associated with osteoarthritis (OA)-related traits through Mendelian randomisation (MR)-based analytical framework. Large-scale two-s le MR was employed to estimate the effects of thousands of plasma proteins on 12 OA-related traits. Additional analyses including Bayesian colocalisation, Steiger filtering analysis, assessment of protein-altering variants and mapping expression quantitative trait loci to protein quantitative trait loci were performed to investigate the reliability of the MR findings protein–protein interaction, pathway enrichment analysis and evaluation of drug targets were conducted to deepen the understanding and identify potential therapeutic targets of OA. Dozens of circulating proteins were identified to have putatively causal effects on OA-related traits, and a majority of these proteins were either drug targets or considered druggable. Through MR analysis, we have identified numerous plasma proteins associated with OA-related traits, shedding light on protein-mediated mechanisms and offering promising therapeutic targets for OA.
Sprifermin: a recombinant human fibroblast growth factor 18 for the treatment of knee osteoarthritis
Publisher: Informa UK Limited
Date: 02-09-2021
Efficacy and safety of GLucocorticoid injections into InfrapaTellar faT pad in patients with knee ostEoarthRitiS: protocol for the GLITTERS randomized controlled trial
Publisher: Springer Science and Business Media LLC
Date: 03-01-2023
DOI: 10.1186/S13063-022-06993-4
Abstract: Knee osteoarthritis (OA) is a prevalent disabling disorder that involves changes in articular cartilage damage, subchondral bone remodeling, synovitis, and abnormal infrapatellar fat pad (IPFP). Due to the complicated etiology and numerous phenotypes of knee OA, limited improvement is achieved for treatments among knee OA patients with different phenotypes. Inflammatory OA phenotype is a typical knee OA phenotype, and in idualized treatment targeting inflammation is a promising way to obtain an optimal therapeutic effect for people with inflammatory knee OA phenotype. Glucocorticoid is a traditional anti-inflammatory drug for knee OA, and intra-articular glucocorticoid injections are recommended clinically. However, emerging evidence has shown that repeated intra-articular glucocorticoid injections in the long term would induce cartilage loss. IPFP and its adjacent synovium are considered as the main source of inflammation in knee OA. This GLITTERS trial aims to investigate if a glucocorticoid injection into the IPFP is effective and safe over 12 weeks among knee OA patients with an inflammatory phenotype. GLITTERS is a multicenter, double-blinded, randomized, and placebo-controlled clinical trial among knee OA patients with both Hoffa-synovitis and effusion-synovitis. Sixty participants will be allocated randomly and equally to either the glucocorticoid group or the control group. Each group will receive an injection of glucocorticoid or saline into the IPFP with an intra-articular hyaluronic acid injection as a background treatment at baseline and be followed at 4, 8, and 12 weeks. The primary outcomes will be changes in knee pain on a visual analog scale and effusion-synovitis volume measured on magnetic resonance imaging (MRI). The secondary outcomes will be changes in the total score of Western Ontario and McMaster Universities Osteoarthritis Index score, MRI-detected Hoffa-synovitis score, quality of life, pain medication use, IPFP volume, and the incidence of adverse reactions. Data analyses based on the intention-to-treat principle will include mixed-effects regressions, Wilcoxon rank-sum tests, and chi-square tests (or Fisher’s exact test). GLITTERS may provide high-quality evidence for the efficacy and safety of ultrasound-guided glucocorticoid injections into IPFP among people with inflammatory knee OA in a short term. The results of this trial are expected to provide a reliable reference for a longer-term risk–benefit profile of this treatment in the future. ClinicalTrials.gov NCT05291650. Registered on 23 March 2022.
Association between Metformin Use and Risk of Total Knee Arthroplasty and Degree of Knee Pain in Knee Osteoarthritis Patients with Diabetes and/or Obesity: A Retrospective Study
Publisher: MDPI AG
Date: 17-08-2022
DOI: 10.3390/JCM11164796
Abstract: Objectives: We aimed to examine whether metformin (MET) use is associated with a reduced risk of total knee arthroplasty (TKA) and low severity of knee pain in patients with knee osteoarthritis (OA) and diabetes and/or obesity. Methods: Participants diagnosed with knee OA and diabetes and/or obesity from June 2000 to July 2019 were selected from the information system of a local hospital. Regular MET users were defined as those with recorded prescriptions of MET or self-reported regular MET use for at least 6 months. TKA information was extracted from patients’ surgical records. Knee pain was assessed using the numeric rating scale. Log-binomial regression, linear regression, and propensity score weighting (PSW) were performed for statistical analyses. Results: A total of 862 participants were included in the analyses. After excluding missing data, there were 346 MET non-users and 362 MET users. MET use was significantly associated with a reduced risk of TKA (prevalence ratio: 0.26, 95% CI: 0.15 to 0.45, p 0.001), after adjustment for age, gender, body mass index, various analgesics, and insurance status. MET use was significantly associated with a reduced degree of knee pain after being adjusted for the above covariates (β: −0.48, 95% CI: −0.91 to −0.05, p = 0.029). There was a significantly accumulative effect of MET use on the reduced risk of TKA. Conclusion: MET can be a potential therapeutic option for OA. Further clinical trials are needed to determine if MET can reduce the risk of TKA and the severity of knee pain in metabolic-associated OA patients.
Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression
Publisher: Elsevier BV
Date: 03-2021
The interactions between MRI-detected osteophytes and bone marrow lesions or effusion-synovitis on knee symptom progression: an exploratory study
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.JOCA.2021.06.008
Abstract: To investigate the longitudinal association between MRI-detected osteophyte scores and progression of knee symptoms, and whether the association was modified in the presence of bone marrow lesions (BMLs) or effusion-synovitis. Data from Vitamin D Effects on Osteoarthritis (VIDEO) study, a randomized, double-blinded and placebo-controlled clinical trial in symptomatic knee osteoarthritis (OA) patients, were analyzed as an exploratory study. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess knee symptoms. Osteophytes, BMLs and effusion-synovitis were measured using MRI. 334 participants with MRI information and WOMAC score (baseline and follow-up) were included in the analyses, with 24.3% of them having knee pain increased 2 years later. Statistically significant interactions were found between MRI-detected osteophytes and BMLs or effusion-synovitis on increased knee symptoms. In participants with BMLs, higher baseline scores of MRI-detected osteophytes in most compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and effusion-synovitis. In participants with effusion-synovitis, higher baseline scores of MRI-detected osteophytes in almost all the compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and BMLs. In contrast, MRI-detected osteophyte scores were generally not associated with knee symptom progression in participants without baseline BMLs or effusion-synovitis. MRI-detected OPs are associated with increased total knee pain, weight-bearing knee pain, stiffness and physical dysfunction in participants presenting BMLs or effusion-synovitis, but not in participants lacking BMLs or effusion-synovitis. This suggests they could interact with bone or synovial abnormalities to induce symptoms in knee OA.
Relative Efficacy and Safety of Anti-Inflammatory Biologic Agents for Osteoarthritis: A Conventional and Network Meta-Analysis
Publisher: MDPI AG
Date: 07-07-2022
DOI: 10.3390/JCM11143958
Abstract: Previous studies have consistently revealed that both local and systemic inflammations are the key to the onset and progression of osteoarthritis (OA). Thus, anti-inflammatory biologic agents could potentially attenuate the progression of OA. We conducted this meta-analysis to examine the efficacy and safety of ant-inflammatory biologic agents among OA patients. Methods: Five databases were searched for randomized controlled trials (RCTs) comparing biologics with placebo or each other in OA patients. Data of pain, physical function, stiffness, and adverse events (AEs) were extracted for a conventional and a Bayesian network meta-analysis. Results: 15 studies with data for 1566 patients were analyzed. In the conventional meta-analysis, etanercept (SMD −0.47 95% CI −0.89, −0.05) and infliximab (SMD −2.04 CI −2.56, −1.52) were superior to placebo for knee pain. In the network meta-analysis, infliximab was superior to all the other biologic agents in improving pain (vs. hyaluronic acid (SMD −22.95 CI −34.21, −10.43), vs. adalimumab (SMD −21.71 CI −32.65, −11.00), vs. anakinra (SMD −24.63 CI −38.79, −10.05), vs. canakinumab (SMD −32.83 CI −44.45, −20.68), vs. etanercept (SMD −18.40 CI −29.93, −5.73), vs. lutikizumab (SMD −25.11 CI −36.47, −14.78), vs. naproxen (SMD −30.16 CI −41.78, −17.38), vs. tocilizumab (SMD −24.02 CI −35.63, −11.86) and vs. placebo (SMD −25.88 CI −34.87, −16.60)). No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. Conclusions: The findings suggest that infliximab may relieve pain more than other biological agents in OA patients. No significant differences were observed between biologics and placebo regarding physical function, stiffness, and risk of AEs. The results must be interpreted cautiously therefore, further randomized controlled trials are warranted.
Quadriceps strength is negatively associated with knee joint structural abnormalities—data from osteoarthritis initiative
Publisher: Springer Science and Business Media LLC
Date: 17-08-2022
DOI: 10.1186/S12891-022-05635-9
Abstract: The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA). This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45–79. Quadriceps strength was measured by isometric knee extension testing at baseline. Knee joint structural abnormalities, including cartilage damage, bone marrow lesions (BMLs), effusion-synovitis and Hoffa-synovitis, were evaluated by Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) at baseline and 1-year follow-up. Generalized estimating equations were employed to examine the associations between quadriceps strength and knee structural abnormalities. All analyses were stratified by sex. One thousand three hundred thirty-eight participants (523 men and 815 women) with a mean age of 61.8 years and a mean BMI of 29.4 kg/m 2 were included in this study. For men, no significantly longitudinal association of quadriceps strength with structural abnormalities was detected. In contrast, quadriceps strength was significantly and negatively associated with changes in cartilage damage and BMLs in lateral patellofemoral joint (PFJ) (cartilage damage: OR : 0.91, 95% CI 0.84 to 0.99, P = 0.023 BMLs: OR : 0.85, 95% CI 0.74 to 0.96, P = 0.011) and effusion-synovitis ( OR = 0.88, 95% CI 0.78 to 0.99, P = 0.045) among females longitudinally. Higher quadriceps strength was significantly associated with less progression of lateral PFJ cartilage damage, BMLs and effusion-synovitis in females. Higher quadriceps strength was associated with changes in cartilage damage and BMLs within the lateral PFJ and effusion-synovitis among females, suggesting the potential protective role of quadriceps strength on joint structures in women.
Synovitis mediates the association between bone marrow lesions and knee pain in osteoarthritis: data from the Foundation for the National Institute of Health (FNIH) Osteoarthritis Biomarkers Consortiu
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.JOCA.2022.06.004
Abstract: Although subchondral bone marrow lesions (BMLs) and synovitis have been well acknowledged as important sources of pain in knee osteoarthritis (KOA), it is unclear if synovitis plays the mediating role in the relationship between BMLs and knee pain. We analyzed 600 subjects with magnetic resonance imaging (MRI) in the Foundation for National Institutes of Health Osteoarthritis Biomarkers Consortium (FNIH) cohort at baseline and 24-month. BMLs and synovitis were measured according to the MRI Osteoarthritis Knee Score (MOAKS) scoring system. BMLs were scored in five subregions. A summary synovitis score of effusion and Hoffa-synovitis was calculated. Knee pain was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Linear regression models were applied to analyze the natural direct effect (NDE) of BMLs and synovitis with knee pain, respectively, and natural indirect effect (NIE) mediated by synovitis. 590 participants (58.8% females, with a mean age of 61.5) were included in the present analyses. For NDE, knee pain was cross-sectionally associated with medial femorotibial BMLs (β = 0.23, 95% CI: 0.09, 0.38) and synovitis (β = 0.40, 95% CI: 0.20, 0.60). Longitudinal associations retained significant [medial femorotibial BMLs (β = 0.37, 95% CI: 0.21, 0.53) synovitis (β = 0.72, 95% CI: 0.45, 0.99)]. In the NIE analyses, synovitis mediated the association between medial femorotibial BML and knee pain at baseline (β = 0.051, 95% CI: 0.01, 0.09) and over 24 months (β = 0.079, 95% CI: 0.023, 0.15), with the mediating proportion of 17.8% and 22.4%, respectively. Synovitis partially mediates the association between medial femorotibial BMLs and knee pain.
Quantitatively Measured Infrapatellar Fat Pad Signal Intensity Alteration is Associated with Joint Effusion-Synovitis in Knee Osteoarthritis
Publisher: Research Square Platform LLC
Date: 13-04-2021
DOI: 10.21203/RS.3.RS-404837/V1
Abstract: Background: Abnormal infrapatellar fat pad (IPFP) plays a detrimental role in knee osteoarthritis (OA) by producing pro-inflammatory cytokines. IPFP may interact with synovium because of their adjacent anatomical positions however, whether abnormal IPFP can contribute to effusion-synovitis in knee OA is unclear.Methods: Among 255 knee OA patients, IPFP signal intensity alteration represented by four measurement parameters [standard deviation of IPFP signal intensity (IPFP sDev), upper quartile value of IPFP high signal intensity region (IPFP UQ (H)), ratio of IPFP high signal intensity region volume to whole IPFP volume (IPFP percentage (H)), and clustering factor of IPFP high signal intensity (IPFP clustering factor (H))] was measured quantitatively at baseline and two-year follow-up using magnetic resonance imaging (MRI). Effusion-synovitis of the suprapatellar pouch and other cavities were measured both quantitatively and semi-quantitatively as effusion-synovitis volume and effusion-synovitis score at baseline and two-year follow-up using MRI. Mixed-effects models were used to assess the associations between IPFP signal intensity alteration and effusion-synovitis over two years.Results: In multivariable analyses, all four parameters of IPFP signal intensity alteration were positively associated with total effusion-synovitis volume and effusion-synovitis volumes of the suprapatellar pouch and of other cavities over two years (all P ＜0.05). They were also associated with the semi-quantitative measure of effusion-synovitis except for IPFP percentage (H) with effusion-synovitis in other cavities. Conclusion: Quantitatively measured IPFP signal intensity alteration is positively associated with joint effusion-synovitis in people with knee OA, suggesting that IPFP signal intensity alteration may contribute to effusion-synovitis and a coexistent pattern of these two imaging biomarkers could exist in knee OA patients.
Longitudinal association of infrapatellar fat pad signal intensity alteration with biochemical biomarkers in knee osteoarthritis
Publisher: Oxford University Press (OUP)
Date: 06-04-2022
DOI: 10.1093/RHEUMATOLOGY/KEAC214
Abstract: To explore the longitudinal association of quantitative infrapatellar fat pad (IPFP) signal intensity alteration with OA-related biomarkers. Eighteen OA-related biochemical biomarkers of 600 knee OA participants in the Foundation for the National Institutes of Health OA Biomarkers Consortium (FNIH) study were extracted. The quantitative IPFP signal intensity measures were acquired based on magnetic resonance imaging, including mean value [Mean (IPFP)] and standard deviation [sDev (IPFP)] of the whole IPFP signal intensity, median value [Median (H)] and upper quartile value [UQ (H)] of high signal intensity, the ratio of volume of high signal intensity to volume of whole IPFP signal intensity [Percentage (H)] and Clustering factor (H). The linear mixed-effect model was applied to determine the longitudinal associations between IPFP signal intensity alteration and biochemical biomarkers over 2 years. All IPFP measures except for Clustering factor (H) were positively associated with urine collagenase-cleaved type II collagen neoepitope (uC2C), urine C-terminal cross-linked telopeptide of type II collagen (uCTX-II), urine C-terminal cross-linked telopeptide of type I collagen-α (uCTX-Iα) and urine N-terminal cross-linked telopeptide of type I collagen (uNTX-I). Mean (IPFP), Median (H) and Percentage (H) were positively associated with the nitrated form of an epitope located in the triple helix of type II collagen (Coll2-1 NO2). Mean (IPFP), Median (H) and UQ (H) were positively associated with sCTX-I and uCTX-Iβ. Positive associations between sDev (IPFP), Percentage (H) and serum hyaluronic acid (sHA) were found. Our results suggest a role of IPFP signal intensity alteration in joint tissue remodelling on a molecular level.
Avoidance of Duplicate Publications From Randomized Clinical Trials
Publisher: American Medical Association (AMA)
Date: 03-12-2020
Osteophytes mediate the associations between cartilage morphology and changes in knee symptoms in patients with knee osteoarthritis
Publisher: Springer Science and Business Media LLC
Date: 08-09-2022
DOI: 10.1186/S13075-022-02905-8
Abstract: To investigate whether the associations between cartilage defects and cartilage volumes with changes in knee symptoms were mediated by osteophytes. Data from the Vitamin D Effects on Osteoarthritis (VIDEO) study were analyzed as a cohort. The Western Ontario and McMaster Universities Osteoarthritis Index was used to assess knee symptoms at baseline and follow-up. Osteophytes, cartilage defects, and cartilage volumes were measured using magnetic resonance imaging at baseline. Associations between cartilage morphology and changes in knee symptoms were assessed using linear regression models, and mediation analysis was used to test whether these associations were mediated by osteophytes. A total of 334 participants (aged 50 to 79 years) with symptomatic knee osteoarthritis were included in the analysis. Cartilage defects were significantly associated with change in total knee pain, change in weight-bearing pain, and change in non-weight-bearing pain after adjustment for age, sex, body mass index, and intervention. Cartilage volume was significantly associated with change in weight-bearing pain and change in physical dysfunction after adjustment. Lateral tibiofemoral and patellar osteophyte mediated the associations of cartilage defects with change in total knee pain (49–55%) and change in weight-bearing pain (61–62%) and the association of cartilage volume with change in weight-bearing pain (27–30%) and dysfunction (24–25%). Both cartilage defects and cartilage volume had no direct effects on change in knee symptoms. The significant associations between cartilage morphology and changes in knee symptoms were indirect and were partly mediated by osteophytes.
The lncRNA PILA promotes NF-κB signaling in osteoarthritis by stimulating the activity of the protein arginine methyltransferase PRMT1.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-05-2022
DOI: 10.1126/SCISIGNAL.ABM6265
Abstract: Inflammatory cytokine-induced activation of nuclear factor κB (NF-κB) signaling plays a critical role in the pathogenesis of osteoarthritis (OA). We identified PILA as a long noncoding RNA (lncRNA) that enhances NF-κB signaling and OA. The abundance of PILA was increased in damaged cartilage from patients with OA and in human articular chondrocytes stimulated with the proinflammatory cytokine tumor necrosis factor (TNF). Knockdown of PILA inhibited TNF-induced NF-κB signaling, extracellular matrix catabolism, and apoptosis in chondrocytes, whereas ectopic expression of PILA promoted NF-κB signaling and matrix degradation. PILA promoted PRMT1-mediated arginine methylation of DExH-box helicase 9 (DHX9), leading to an increase in the transcription of the gene encoding transforming growth factor β-activated kinase 1 (TAK1), an upstream activator of NF-κB signaling. Furthermore, intra-articular injection of an adenovirus vector encoding PILA triggered spontaneous cartilage loss and exacerbated posttraumatic OA in mice. This study provides insight into the regulation of NF-κB signaling in OA and identifies a potential therapeutic target for this disease.
Response to: ‘Infrapatellar fat pad resection during total knee replacement: yet another reason?’ by Ryan
Publisher: BMJ
Date: 27-06-2018
Associations between knee structural measures, circulating inflammatory factors and MMP13 in patients with knee osteoarthritis
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.JOCA.2018.05.003
Abstract: To investigate cross-sectional associations between serum level of Matrix metalloproteinase (MMP)13 and knee structural measures and circulating inflammatory factors in patients with symptomatic knee osteoarthritis (OA). A total of 149 subjects with symptomatic knee OA were included. Magnetic resonance imaging was used to measure infrapatellar fat pad (IPFP) volume, IPFP signal intensity alternation, cartilage volume and cartilage defects. Knee radiography was used to assess radiographic OA using the Kellgren-Lawrence (K-L) grading system. Enzyme-linked immunosorbent assay was used to measure the serum levels of inflammatory factors and MMP13. In multivariable analyses, serum MMP13 was negatively associated with cartilage volume at patellar site (β: -32.94 mm Serum level of MMP13 was associated with knee structural abnormalities as well as serum inflammatory factors. These suggest that systemic MMP13 may play a role in knee OA, and could be regulated by inflammatory factors.
Metformin use and associated risk of total joint replacement in patients with type 2 diabetes: a population-based matched cohort study
Publisher: CMA Impact Inc.
Date: 18-12-2022
DOI: 10.1503/CMAJ.220952
Osteoarthritic infrapatellar fat pad aggravates cartilage degradation via activation of p38MAPK and ERK1/2 pathways
Publisher: Springer Science and Business Media LLC
Date: 25-09-2021
DOI: 10.1007/S00011-021-01503-9
Abstract: This study aimed to investigate the biochemical effects of osteoarthritic infrapatellar fat pad (IPFP) on cartilage and the underlying mechanisms. Human IPFP and articular cartilage were collected from end-stage osteoarthritis (OA) patients during total knee arthroplasty. IPFP-derived fat-conditioned medium (FCM) was used to stimulate human primary chondrocytes and cartilage explants. Functional effect of osteoarthritic IPFP was explored in human primary chondrocytes and articular cartilage in vitro and ex vivo. Activation of relative pathways and its effects on chondrocytes were assessed through immunoblotting and inhibition experiments, respectively. Neutralization test was performed to identify the main factors and their associated pathways responsible for the effects of IPFP. Osteoarthritic IPFP-derived FCM significantly induced extracellular matrix (ECM) degradation in both human primary chondrocytes and cartilage explants. Several pathways, such as NF-κB, mTORC1, p38MAPK, JNK, and ERK1/2 signaling, were significantly activated in human chondrocytes with osteoarthritic IPFP-derived FCM stimulation. Interestingly, inhibition of p38MAPK and ERK1/2 signaling pathway could alleviate the detrimental effects of FCM on chondrocytes, while inhibition of other signaling pathways had no similar results. In addition, IL-1β and TNF-α instead of IL-6 in osteoarthritic IPFP-derived FCM played key roles in cartilage degradation via activating p38MAPK rather than ERK1/2 signaling pathway. Osteoarthritic IPFP induces the degradation and inflammation of cartilage via activation of p38MAPK and ERK1/2 pathways, in which IL-1β and TNF-α act as the key factors. Our study suggests that modulating the effects of IPFP on cartilage may be a promising strategy for knee OA intervention.
Osteophytes mediate the associations between cartilage morphology and changes in knee symptoms in patients with knee osteoarthritis
Publisher: Research Square Platform LLC
Date: 18-05-2022
DOI: 10.21203/RS.3.RS-1663778/V1
Abstract: Aims: To investigate whether the associations between cartilage defects and cartilage volumes with changes in knee symptoms were mediated by osteophytes. Methods: Data from Vitamin D Effects on Osteoarthritis (VIDEO) study were analyzed as a cohort. Western Ontario and McMaster Universities Osteoarthritis Index was used to assess knee symptoms at baseline and follow-up. Osteophytes, cartilage defects and cartilage volumes were measured using magnetic resonance imaging at baseline. Associations between cartilage morphology and changes in knee symptoms were assessed using linear regression models, and mediation analysis was used to test whether these associations were mediated by osteophytes. Results: 334 participants (aged 50 to 79 years) with symptomatic knee osteoarthritis were included in the analysis. Cartilage defects were significantly associated with change in total knee pain, change in weight-bearing pain and change in non-weight-bearing pain after adjustment for age, sex, body mass index and intervention. Cartilage volume was significantly associated with change in weight-bearing pain and change in physical dysfunction after adjustment. Lateral tibiofemoral and patellar osteophyte mediated: the associations of cartilage defects with change in total knee pain (49%-55%) and change in weight-bearing pain (61%-62%) the association of cartilage volume with change in weight-bearing pain (27%-30%) and dysfunction (24%-25%). Both cartilage defects and cartilage volume had no direct effects on change in knee symptoms. Conclusions: The significant associations between cartilage morphology and changes in knee symptoms were indirect and were partly mediated by osteophytes.
Associations between diet quality and knee joint structures, symptoms and systemic abnormalities in people with symptomatic knee osteoarthritis.
Publisher: Elsevier BV
Date: 05-2021
Related Organisations
Guangzhou First People’s Hospital, School Of Medicine, South China University Of Technology
Location: China
Related Funding Activities
No related grants have been discovered for GUANGFENG RUAN.