ORCID Profile
0000-0001-6306-0818
Current Organisations
Taipei Municipal Wan-Fang Hospital
,
Taipei Medical University
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.
Publisher: American Chemical Society (ACS)
Date: 13-09-2021
Abstract: Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth. The gelatin-based conduits mimicked the fascicular architecture of natural nerve ECM. The multichanneled (MC) scaffolds, cross-linked with microbial transglutaminase, possessed sustainable mechanical stability. Meanwhile, the release profile of dual neurotrophic factors, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), exhibited a temporal-controlled manner. In vitro, the differentiated neural stem cells effectively extended their neurites along the aligned nanofibers. Besides, in the treated group, the cell density increased in high NGF concentration regions of the gradient membrane, and the BDNF significantly promoted myelination. In a rabbit sciatic nerve transection in vivo model, the MC/AN/NG scaffold showed superior nerve recovery and less muscle atrophy comparable to autograft. By integrating multiple strategies to promote peripheral nerve regeneration, the MC/AN/NG scaffolds as nerve guidance conduits showed promising results and efficacious treatment alternatives for autologous nerve grafts.
Publisher: Springer Science and Business Media LLC
Date: 15-07-2014
Publisher: Wiley
Date: 14-10-2010
DOI: 10.1111/J.1525-1594.2010.01086.X
Abstract: The effects of low intensity pulsed ultrasound to tenocytes and osteocytes are well understood and applied clinically. However, its effects on cultured Schwann cells are still not well elucidated. This study was designed to elucidate the effects of low intensity pulsed ultrasound on cultured Schwann cells and their possible molecular mechanism. Schwann cells were harvested from sciatic nerves of 3-day-old Sprague-Dawley rats. Low intensity pulsed ultrasound stimulator (frequency: 1 MHz, duration: 2 min, duty cycle: 20%, total treatment time: 3 min) was applied to three different culture conditions: regular culture medium containing 0, 5, or 10% fetal bovine serum. The viability, damage, and differentiation of Schwann cells were examined gene expression was also analyzed. In the presence of 0.3 W/cm(2) pulsed ultrasound stimulation, increases in cell viability and decreases in cell apoptosis were observed in the serum deprivation group in this culture condition, interleukin-1, tumor necrosis factor-alpha, and protein zero genes expression were downregulated and Desert Hedgehog transcripts gene expression was upregulated. We concluded that intervention with low intensity pulsed ultrasound could promote Schwann cell proliferation, prevent cell death, and keep adequate phenotype presentation for peripheral nerve recovery. The low intensity pulsed ultrasound stimulation to an injured nerve site could be applied as early as possible especially when the microenvironment is almost serum-free to obtain the most benefit.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-05-2009
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JFMA.2013.09.015
Abstract: Genomic studies have revealed that there is a significant association between a point mutation of the human Col2A1 gene (G1170S) and several hip disorders. The purpose of the study was to explore the phenotype and altered cartilage matrix homeostasis of transgenic mice carrying this mutated Col2a1 gene. Wild-type and transgenic mice were used as the control and study groups, respectively. Body weight measurement, radiographic analysis, and histological analysis of the mice were carried out to describe differences between the wild-type and transgenic mice at different ages. Cartilage metabolism studies were also carried out, including an MTT assay of cellular proliferation and nitric oxide and glycosaminoglycan assays. Allelic expression levels of the mutant A allele and the normal G allele were established by TaqMan assay. Cytokine and protease gene expression were measured. Transgenic mice had a lower mean body weight, a deformed skeletal structure, and abnormal cartilage histomorphology. Chondrocyte proliferation was significantly compromised and this was linked to significantly higher NO secretion and less soluble glycosaminoglycan formation. TNF-α and IL-1β gene expression was significantly upregulated, while MMP-13 gene expression was significantly downregulated. The mutant G1170S Col2a1 gene in mice clearly alters the transgenic murine phenotype and cartilage matrix homeostasis.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.NUTRES.2010.03.004
Abstract: Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase, which catalyzes the conversion of 3-hydroxy-3-methylglutaryl-coenzyme A to mevalonate, a rate-limiting step in cholesterol synthesis. Statins are able to reduce cardiovascular risk in hypercholesterolemic patients. In recent years, the possible effect of statins on bone tissue has received particular attention. The present study was undertaken to understand the events of osteoblast differentiation induced by statins. Our hypothesis is that simvastatin promotes osteoblast viability and differentiation via Ras/Smad/Erk/bone morphogenic protein (BMP)-2 signaling pathway. The viability and differentiation of osteoblasts were examined by mitochondrial activity assay, alkaline phosphatase (ALP) activity, and gene expression. The associated signaling pathways were analyzed by cytoplasmic and membrane proteins manifestation. After administration of 10(-6) M simvastatin, the ALP activity was significantly enhanced, and the expression of BMP-2, ALP, sialoprotein, and type I collagen genes were up-regulated. After simvastatin treatment, both the RasGRF1 and phospho-RasGRF1 in the cytoplasm decreased significantly, whereas those on the plasma membrane increased. A marked increase in membranous GAP-associated protein (P190) and the activated form of both phospho-extracellular signal-regulated kinase1/2 and phospho-Smad1 were also noted. In conclusion, this study shows that statins pose a positive effect on the metabolism of osteoblasts. Simvastatin can promote osteoblast viability and differentiation via membrane-bound Ras/Smad/Erk/BMP-2 pathway. Statins stimulate osteoblast differentiation in vitro and may be a promising drug for the treatment of osteoporosis in the future.
Publisher: Springer Science and Business Media LLC
Date: 18-09-2014
DOI: 10.1007/S10103-014-1658-5
Abstract: For decades, low-level laser therapy (LLLT) has widespread applications in tendon-related injuries. Although the therapeutic effect of LLLT could be explained by photostimulation of target tissue and cells, how tenocytes sense photonic energy and convert them into cascades of cellular and molecular events is still not well understood. This study was designed to elucidate the effects of LLLT on cell proliferation and collagen synthesis by examining the associated second messengers including ATP, Ca(2+), and nitric oxide using rat Achilles tenocytes. Moreover, proliferating cell nuclear antigen (PCNA) and transforming growth factor-β1 (TGF-β1) related to cell proliferation and matrix metabolism were also studied. The results showed that 904 nm GaAs laser of 1 J/cm(2) could significantly increase the MTT activity and collagen synthesis of tenocytes. Second messengers including ATP and intracellular Ca2+ were increased after laser treatment. Quantitative PCR analysis of tenocytes treated with laser revealed up-regulated expression of PCNA, type I collagen, and TGF-β1. Besides, laser-induced TGF-β1 expression was significantly inhibited by extracellular signal-regulated kinase (ERK) specific inhibitor (PD98059). The findings suggested that LLLT stimulated ATP production and increased intracellular calcium concentration. Directly or indirectly via production of TGF-β1, these second messengers mediated the proliferation of tenocytes and synthesis of collagen.
Publisher: Informa UK Limited
Date: 24-07-2012
DOI: 10.3109/03008207.2012.685132
Abstract: Inflammation has been proposed to be an important causative factor in ligamentum flavum hypertrophy. However, the mechanisms of mechanical load on inflammation of ligamentum flavum remain unclear. In this study, we used an in vitro model of human ligamentum flavum fibroblasts subjected to centrifugal force to elucidate the effects of mechanical load on cultured human ligamentum flavum fibroblasts we further studied its molecular and biochemical mechanisms. Human ligamentum flavum fibroblasts were obtained from six patients undergoing lumbar spine surgery. Monolayer cultures of human ligamentum flavum fibroblasts were subjected to different magnitudes of centrifugal forces. Cell viability, cell death, biochemical response, and molecular response to centrifugal forces were analyzed. It was found that centrifugal stress significantly suppressed cell viability without inducing cell death. Centrifugal force at 67.1 g/cm(2) for 60 min significantly increases the production of prostaglandin E2 and nitric oxide as well as gene expression of proinflammatory cytokines, including interleukin (IL)-1α, IL-1β and IL-6, showed that centrifugal force-dependent induction of cyclooxygense-2 and inducible NO synthase required JNK and p38 mitogen-activated protein kinase, but not ERK 1/2 activities. This study suggested that centrifugal force does induce inflammatory responses in human ligamentum flavum fibroblasts. The activation of both JNK and p38 mitogen-activated protein kinase mechanotransduction cascades is a crucial intracellular mechanism that mediates cyclooxygense-2 rostaglandin E2 and inducible NO synthase/nitric oxide production.
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.NUTRES.2009.10.020
Abstract: Septic arthritis is an inflammatory arthropathy characterized by degeneration of articular cartilage. Icariin, the main active flavonoid glucoside isolated from Epimedium pubescens, is used as antirheumatics (or antiinflammatory), tonics, and aphrodisiacs in traditional Chinese medicine. In this study, we used lipopolysaccharide (LPS) to simulate the in vitro inflammatory response of chondrocytes during septic arthritis. Our hypothesis is that the icariin can protect chondrocytes from LPS-induced inflammation and extracellular matrix degradation. The inflammation of neonatal mice chondrocytes was induced by LPS and the antiinflammatory effects were examined. The synthesis of nitric oxide was analyzed, whereas the titer of glycosaminoglycan and total collagen were measured and the gene expressions (including inducible nitric oxide synthase [iNOS], matrix metalloproteinase [MMP]-1, MMP-3, and MMP-13) were evaluated. The results showed that the viability of chondrocytes, extracellular matrix synthesis, was significantly decreased, whereas nitric oxide synthesis was significantly increased in the presence of 10(-5) g/mL LPS. Icariin pretreatment can partially reverse these effects. The up-regulated expressions of MMP-1, 3, 13, cyclooxygenase-2 (COX-2), and iNOS genes by LPS treatment were also significantly down-regulated by the pretreatment of icariin to 1.8%, 0.056%, 7.7%, 3.1%, and 5.3% of the LPS-positive control s le, respectively. Our results demonstrate that icariin is a safe anabolic agent of chondrocytes. Icariin may exert its protective effects through inhibition of nitric oxide and MMP synthesis, and may then reduce the extracellular matrix destruction.
Publisher: Springer Science and Business Media LLC
Date: 20-03-2015
DOI: 10.1007/S10856-015-5478-3
Abstract: Hyaluronic acid-based hydrogels can reduce postoperative adhesion. However, the long-term application of hyaluronic acid is limited by tissue mediated enzymatic degradation. To overcome this limitation, we developed a polygalacturonic acid and hyaluronate composite hydrogel by Schiff's base crosslinking reaction. The polygalacturonic acid and hyaluronate composite hydrogels had short gelation time (less than 15 s) and degraded by less than 50 % in the presence of hyaluronidase for 7 days. Cell adhesion and migration assays showed polygalacturonic acid and hyaluronate composite hydrogels prevented fibroblasts from adhesion and infiltration into the hydrogels. Compared to hyaluronate hydrogels and commercial Medishield™ gels, polygalacturonic acid and hyaluronate composite hydrogel was not totally degraded in vivo after 4 weeks. In the rat laminectomy model, polygalacturonic acid and hyaluronate composite hydrogel also had better adhesion grade and smaller mean area of fibrous tissue formation over the saline control and hyaluronate hydrogel groups. Polygalacturonic acid and hyaluronate composite hydrogel is a system that can be easy to use due to its in situ cross-linkable property and potentially promising for adhesion prevention in spine surgeries.
Publisher: IOP Publishing
Date: 07-06-2016
DOI: 10.1088/1748-6041/11/3/035010
Abstract: Extensive epidural fibrosis is a common complication following spinal surgery and can cause pain and limited mobility. In the present study, a novel biomimetic approach was developed to prevent postsurgical adhesion of the dura. We aimed to reconstruct epidural fat, which prevents scar-tissue adhesion, through the development of an injectable decellularized adipose matrix (DAM)-containing hyaluronic acid (HA) hydrogel loaded with adipose stromal cells (ASCs). Injectable DAM was prepared from porcine adipose tissue by four freeze-thaw cycles with subsequent pepsin digestion. Residual analyses confirmed the efficacy of detergent-free decellularization, while most sulfated glycosaminoglycans and collagen were preserved. The Transwell migration assay demonstrated the anti-infiltrative property of the DAM-containing HA hydrogel. After 14 d of 3D culture, the DAM-containing HA hydrogel showed inductive potential in the adipogenic differentiation of ASCs. For an in vivo study, the ASC-loaded DAM-containing HA hydrogel (DAM/ASC-incorporated HA hydrogel) was injected into adult laminectomized male rats, and the results were assessed by microscopic histological examination. The in vivo data indicated that HA hydrogel, DAM, and ASCs were all required for the ability of the engineered fat tissue to block the invasion of the fibrous tissue. Our results suggested that this injectable DAM/ASC-incorporated HA hydrogel has potential applications in minimally invasive surgery for soft-tissue reconstruction and epidural fibrosis prevention.
Publisher: Informa UK Limited
Date: 30-11-2010
DOI: 10.3109/03008207.2010.525673
Abstract: Ultrasound is an effective noninvasive treatment for various tendinopathies. However, how tenocytes convert ultrasound stimulation into cascades of cellular and molecular events is not well understood. The purpose of this study is to elucidate the signaling pathways of tenocytes during ultrasound stimulation. Primary cultures of tenocytes were harvested from Achilles tendons of Sprague-Dawley rats. The viability and proliferation of tenocytes, their genes expression, and the signaling pathways after ultrasound treatment with or without specific inhibitors were evaluated and analyzed. The results showed that ultrasound treatment (100 mW/cm(2) for 20 min) significantly enhanced matrix metalloproteinase 13 (MMP-13), c-Fos, and c-Jun gene expression, increased JNK and p38, but not extracellular signal-regulated kinase-1/2 (ERK1/2), phosphorylation at 5 min, and sustained up to 60 min. JNK inhibitor and p38 inhibitor, but not ERK1/2 inhibitor, attenuated ultrasound-dependent induction of MMP-13 expression, indicating that the JNK and p38 pathways are required for ultrasound-induced MMP-13 expression in tenocytes. We also found that SB431542 (transforming growth factor-beta (TGF-β) receptor kinases inhibitor) suppressed ultrasound-induced MMP?13 and c-Fos gene expression, and p38 phosphorylation. This study revealed that ultrasound treatment stimulates tenocytes proliferation and regulates their matrix metabolism through the cross-talk between TGF-β and ultrasound-induced mitogen-activated protein kinases (MAPKs) signaling pathways.
Publisher: Walter de Gruyter GmbH
Date: 2020
Abstract: Peripheral nerve injury is a life-changing disability with significant socioeconomic consequences. In this rat model, we propose that partial enzyme digestion can facilitate the functional recovery of a crushed nerve. The sciatic nerves were harvested and in vitro cultured with the addition of Liberase to determine the appropriate enzyme amount in the hyaluronic acid (HA) membrane. Then, the sciatic nerve of adult male Sprague-Dawley rats was exposed, crushed, and then treated with partial enzyme digestion (either 0.001 or 0.002 unit/mm 2 Liberase-HA membrane). The sciatic function index (SFI) for functional recovery of the sciatic nerve was evaluated. After 2 h of in vitro digestion, fascicles and axons were separated from each other, with the cells mobilized. Greater destruction of histology structures occurred in the high enzyme (Liberase-HA membrane at 0.002 unit/mm 2 ) group at 24 h than in the low enzyme (0.001 unit/mm 2 ) group at 48 h. In the SFI evaluation, the improvement in 0.001 unit/mm 2 Liberase group was significantly better than control and 0.002 unit/mm 2 Liberase group. Our study demonstrated that appropriate enzyme digestion had a significantly faster and earlier recovery.
Publisher: Informa UK Limited
Date: 24-07-2012
DOI: 10.3109/03008207.2012.679368
Abstract: The formation of fibrotic tissue in the ligamentum flavum (LF) is usually preceded by breakdown of elastic fibers. Elastin-derived peptides (EDPs) from breakdown of elastic fibers display a wide range of biological activities in a variety of cells, but there is minimal information regarding the involvement in the processes of LF hypertrophy. The aim of this study is to elucidate the effects of EDPs on cultured human LF cells and to investigate their molecular and biochemical mechanisms. Human LF cells were obtained from 18 patients who underwent lumbar spine surgery. After treatment with different concentrations of EDPs with or without specific inhibitors in culture medium, the viability and proliferation of LF cells, genes expression, and the signaling pathways were evaluated and analyzed. It was found that 50 μg/ml EDPs significantly increased cell proliferation and synthesis of prostaglandin E(2). The gene expression and protein production of proinflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, and IL-6, were also upregulated. The levels of p-ERK (extracellular signal-regulated kinase) and NF-κB increased immediately following EDP treatment and sustained up to 90 min. It was also found that NF-κB inhibitor, but not ERK1/2 inhibitor, attenuated EDP-dependent induction of IL-1α, IL-1β, and IL-6 expression, indicating that NF-κB pathways are required for EDP-induced IL-1α, IL-1β, and IL-6 gene expression in human LF cells. The results of this in vitro experiment suggest that EDPs do induce inflammatory responses in human LF cells and plays the key role in the development of LF hypertrophy.
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.PHYMED.2009.08.007
Abstract: Epimedii herba is one of the most frequently used herbs in formulas prescribed for the treatment of osteoporosis in China. The main active flavonoid glucoside extracted from Epimedium pubescens is Icariin, which has been reported to enhance bone healing and reduce osteoporosis occurrence. However, the detailed molecular mechanisms remain unclear. In this present study, we examine the molecular mechanisms of icariin by using primary osteoblast cell cultures obtained from adult mice. The osteoblast cells were harvested from 8-month old female Imprinting Control Region (ICR) mice. The effects of icariin stimulation on the proliferation, differentiation and maturation of osteoblasts were examined. The production of nitric oxide (NO) and caspase-3 were analyzed, along with the gene expressions of bone morphogenetic protein-2 (BMP-2), SMAD4, Cbfa1/Runx2, OPG, and RANKL. The viability of the osteoblasts reached its maximum at 10(-8)M icariin. At this concentration, icariin increased the proliferation and matrix mineralization of osteoblasts and promoted NO synthesis. With icariin treatment, the BMP-2, SMAD4, Cbfa1/Runx2, and OPG gene expressions were up-regulated the RANKL gene expression was however down-regulated. Concurrent treatment involving the BMP antagonist (Noggin) or the NOS inhibitor (L-NAME) diminished the icariin-induced cell proliferation, ALP activity, NO production, as well as the BMP-2, SMAD4, Cbfa1/Runx2, OPG, RANKL gene expressions. In this study, we demonstrate that in vitro icariin is a bone anabolic agent that may exert its osteogenic effects through the induction of BMP-2 and NO synthesis, subsequently regulating Cbfa1/Runx2, OPG, and RANKL gene expressions. This effect may contribute to its action on the induction of osteoblasts proliferation and differentiation, resulting in bone formation.
Publisher: Elsevier BV
Date: 11-2004
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.ULTRASMEDBIO.2007.11.002
Abstract: The shock wave is an effective noninvasive modality for resolving various tendon pathologies. However, scientific rationale and mechanism of shock wave therapy remains limited. This study aims to investigate the effects of shock waves and their biochemical mechanisms on tenocyte proliferation and collagen synthesis. Tenocytes harvested from Achilles tendons of Sprague-Dawley rats were used in this study. Cell viability was assayed by trypan blue exclusion methods. The colorimetric assay was determined to evaluate the mitochondria activity of the tenocytes after shock wave exposure. Synthesis of collagen, nitric oxide (NO) and transforming growth factor-beta1 (TGF-beta1) were determined and their gene expression was also studied. The results showed that there was a dose-dependent impairment of cell viability observed in 0.36 mJ/mm2 and 0.68 mJ/mm2 stimulation. In the proliferation assay, low energy level with low impulses (0.36 mJ/mm2 with 50 and 100 impulses) showed positive stimulatory effects, whereas the high energy level with high impulses (0.68 mJ/mm2 with 250 and 500 impulses) had significant inhibitory effects. At 0.36 mJ/mm2, 100 impulse shock waves treatment, up-regulation of proliferating cell nuclear antigen (PCNA) (at 6 and 24 h) and collagen type I, collagen type III and TGF-beta1 gene expression (at 24 h) were observed these were followed by the increases in NO production (at 24 h), TGF-beta1 release (at 48 and 96 h) and collagen synthesis (at the 7th day). This study revealed that shock waves can stimulate tenocyte proliferation and collagen synthesis. The associated tenocyte proliferation is mediated by early up-regulation of PCNA and TGF-beta1 gene expression, endogenous NO release and synthesis and TGF-beta1 protein and then collagen synthesis.
Publisher: Informa UK Limited
Date: 06-03-2015
DOI: 10.3109/03008207.2015.1016609
Abstract: There are limited strategies to restore the damaged annulus fibrosus (AF) of the intervertebral disc. Low-intensity pulsed ultrasound (LIPUS) has positive effects on the proliferation of several types of cells and the repair of damage tissue in vivo. However, scientific evidence of therapeutic effects of LIPUS on AF cells remains limited. The purpose of this study is to evaluate the feasibility of applying LIPUS to the repair of the AF. We used an in vitro model of human AF cells subjected to LIPUS stimulation to examine its effects on cell proliferation and matrix metabolism. Cell viability, synthesis of collagen and glycosaminoglycan (GAG), expression of matrix metalloproteinases (MMPs) and transforming growth factor β1 and pathways involving mitogen-activated protein kinases (MAPKs) were investigated. LIPUS significantly enhanced proliferation of AF cells after 5 days of treatment. LIPUS with an intensity of 0.5 W/cm(2) increased the collagen and GAG synthesis and decreased the expressions of MMP-1 and -3 of human AF cells. Real-time polymerase chain reactions and western blotting analysis revealed that LIPUS could increase transforming growth factor β1 (TGF-β1) and activate extracellular signal-regulated kinase (ERK) pathway. In addition, TGF-β receptor kinase inhibitor could suppress the ultrasound-induced alterations in cell viability and matrix metabolism. The findings suggested that LIPUS could be useful as a physical stimulation of cell metabolism for the repair of the AF.
Publisher: SAGE Publications
Date: 03-2016
Abstract: The formation of fibrous tissue is part of the natural healing response following a laminectomy. Severe scar tissue adhesion, known as epidural fibrosis, is a common cause of failed back surgery syndrome. In this study, by combining the advantages of drug treatment with a physical barrier, an ibuprofen-conjugated crosslinkable polygalacturonic acid and hyaluronic acid hydrogel was developed for epidural fibrosis prevention. Conjugation was confirmed and measured by 1D 1 H NMR spectroscopy. In vitro analysis showed that the ibuprofen-conjugated polygalacturonic acid–hyaluronic acid hydrogel showed low cytotoxicity. In addition, the conjugated ibuprofen decreased prostaglandin E 2 production of the lipopolysaccharide-induced RAW264.7 cells. Histological data in in vivo studies indicated that the scar tissue adhesion of laminectomized male adult rats was reduced by the application of our ibuprofen-conjugated polygalacturonic acid-hyaluronic acid hydrogel. Its use also reduced the population of giant cells and collagen deposition of scar tissue without inducing extensive cell recruitment. The results of this study therefore suggest that the local delivery of ibuprofen via a polygalacturonic acid-hyaluronic acid-based hydrogel reduces the possibility of epidural fibrosis.
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.BIOMATERIALS.2018.05.009
Abstract: The poor regenerative capability of stem cell transplantation in the central nervous system limits their therapeutic efficacy in brain injuries. The sustained inflammatory response, lack of structural support, and trophic factors deficiency restrain the integration and long-term survival of stem cells. Instead of exogenous stem cell therapy, here we described the synthesis of nanohybrid hydrogel containing sulfated glycosaminoglycan-based polyelectrolyte complex nanoparticles (PCN) to mimic the brain extracellular matrix and control the delivery of stromal-derived factor-1α (SDF-1α) and basic fibroblast factor (bFGF) in response to matrix metalloproteinase (MMP) for recruiting endogenous neural stem cells (NSC) and regulating their cellular fate. Bioactive factors are delivered by electrostatic sequestration on PCN to lify the signaling of SDF-1α and bFGF to regulate NSC in vitro. In in vivo ischemic stroke model, the factors promoted neurological behavior recovery by enhancing neurogenesis and angiogenesis. These combined strategies may be applied for other tissue regenerations by regulating endogenous progenitors through the delivery of different kinds of glycosaminoglycan-binding molecules.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.PHYMED.2010.04.003
Abstract: Icariin has been reported to enhance bone healing and treat osteoporosis. In this study, we examined the detail molecular mechanisms of icariin on lipopolysaccharide (LPS)-induced osteolysis. Our hypothesis is that icariin can inhibit osteoclast differentiation and bone resorption by suppressing MAPKs/NF-κB regulated HIF-1α and PGE(2) synthesis. After treatment with icariin, the activity of osteoclasts differentiation maker, tatrate resistances acid phosphatease (TRAP), significantly decreased at the concentration of 10(-8)M. Icariin (10(-8)M) reduced the size of LPS-induced osteoclasts formation, and diminished their TRAP and acid phosphatease (ACP) activity without inhibition of cell viability. Icariin also inhibited LPS-induced bone resorption and interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression. The gene expression of osteoprotegerin (OPG) was up-regulated, while receptor activator of NF-κB ligand (RANKL) was down-regulated. Icariin also inhibited the synthesis of cyclo-oxygenase type-2 (COX-2) and prostaglandin E(2) (PGE(2)). In addition, icariin had a dominant repression effect on LPS-induced hypoxia inducible factor-1α (HIF-1α) expression of osteoclasts. On osteoclasts, icariin suppresses LPS-mediated activation of the p38 and JNK while on the osteoblasts, icariin reduced the LPS-induced activation of ERK1/2 and I-kappa-B-alpha (IκBα), but increased the activation of p38. In conclusion, we demonstrated that icariin has an in vitro inhibitory effects on osteoclasts differentiation that can prevent inflammatory bone loss. Icariin inhibited LPS-induced osteoclastogenesis program by suppressing activation of the p38 and JNK pathway.
Location: Taiwan, Province of China
No related grants have been discovered for Ming-Hong Chen.