Understanding Skeletal Development: A Non-proteolytic Mechanism Of Aggrecan Resorption In The Growth Plate
Funder
National Health and Medical Research Council
Funding Amount
$563,044.00
Summary
Bone formation requires resorption of a cartilage template. We challenge the dogma that cartilage resorption is only by PROTEASES, and propose instead that GLYCOSIDASES might also be involved. Aims: Demonstrate that chondrocytes release glycosidases that are important for bone formation. Significance: New information for the design of reconstructive therapies for people with congenital and acquired limb deficiencies or inherited disorders such as arthritis and chondrodysplasias may be gained.
Roles Of Injury-induced Inflammatory Response In Regulating Bony Repair At Injured Growth Plate Cartilage
Funder
National Health and Medical Research Council
Funding Amount
$366,301.00
Summary
Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, w ....Children's growth plate cartilage is responsible for bone lengthening. Due to popularity of sports and play, trauma-induced growth plate damage and subsequently bone growth defects are common in children, with up to 30% of growth plate injury cases resulting in growth abnormality, for which the present surgical correction is highly invasive and not fully effective. Although we know that the growth plate injury-induced bone growth defects result from bony repair of the injured growth cartilage, we largely don't understand why and how this bony repair occurs. Understanding mechanisms for this faulty bony repair of injured growth plate will be critical prior to effective biological treatments can be developed. Recently, using an injury model in young rats, we found that bony tissue formation at injured growth plate is preceded sequentially by inflammatory, fibrogenic, chondrogenic and osteogenic responses. The inflammatory response is an initial event and our recent studies suggest that inflammatory response recruits inflammatory cells and produces important molecules that could significantly influence subsequent fibrogenic, chondrogenic and osteogenic events leading to the bony repair of the injured growth plate cartilage. The current proposal further addresses roles of the inflammatory response and the molecular pathways of this response in regulating downstream bony repair events. This project will generate novel understanding on the faulty bony repair of injured growth plate, and will provide valuable information for developing cost-effective and simple therapeutic intervention that aims to prevent bony repair and to enhance cartilage regeneration of the injured growth plate in children.Read moreRead less
Pathophysiology And Prevention Of Methotrexate Chemotherapy-induced Bone Growth Defects
Funder
National Health and Medical Research Council
Funding Amount
$622,598.00
Summary
Childhood chemotherapy often causes growth arrest, osteoporosis, and fractures in cancer patients and survivors. Using a rat model, this project will study how the most commonly used chemotherapy drug methotrexate causes bone growth defects and examine any protective effects of two natural-derived substances. This work will increase our knowledge on chemotherapy-induced bone growth defects, and will be useful for developing a preventative treatment.
Bone Growth For Healthy Development: Physiology, Pathophysiology, And Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$621,458.00
Summary
Musculoskeletal damage is a major burden on individuals and our health care system. My research program will focus on improving bone health in three important areas: (1) children’s growth plate injury and growth defects; (2) bone loss and bone marrow defects from cancer chemotherapy; (3) ensuring that bone grows healthily in early life. The overall intent of this research is to develop new therapies when bone doesn’t grow well, or is damaged.
Mobilisation Of Endogenous Mesenchymal Progenitor Cells For Growth Plate Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$605,251.00
Summary
Growth plate cartilage is responsible for bone growth in children. Its injury is common and is often repaired undesirably by bony tissue which causes significant bone growth defects. This project will develop a biological treatment through mobilising endogenous progenitor cells to enhance growth plate regeneration and prevent bone growth defects, which will allow patients to avoid highly invasive/costly corrective surgeries.
Sclerostin And Dickkopf-1 In Regulation Of Bone Mass
Funder
National Health and Medical Research Council
Funding Amount
$638,581.00
Summary
The WNT pathway is a powerful regulator of bone cell differentiation and bone formation. Two WNT modulators, sclerostin ad Dickkopf 1, are being developed for therapy in bone disease, but critical questions remain unanswered. In this study we use unique genetic mouse models created by the applicants to resolve specific deficiencies surrounding their actions and application as therapies.
NT-3 As An Upstream And Potentially Master Regulator Promoting Bone Fracture Healing
Funder
National Health and Medical Research Council
Funding Amount
$712,857.00
Summary
There is a strong clinical need for cost-effective treatments for delayed healing or non-union bone fractures. Our recent data suggest injury site-derived neurotrophin-3 (NT-3) may be an important overall regulator of bone repair by inducing key factors involved in fracture callus formation and remodelling. This project will address roles and mechanisms of endogenous NT-3 in bone repair and the likelihood of exogenous NT-3 protein in promoting bone healing in clinically relevant fracture models.
“I am a biomedical scientist undertaking basic and clinical research on the pathophysiology of growth plate injury and repair, which critically impacts on children’s bone growth and growth disorders. I aim to investigate the underlying mechanisms and deve
Osteal Macrophages: Novel Regulators Of Osteoblast Function And The Endosteal Stem Cell Niche
Funder
National Health and Medical Research Council
Funding Amount
$406,125.00
Summary
Bone diseases are a major health problem and current treatments are inadequate. We are investigating a novel role for macrophages (cells important in tissue maintenance and immune responses) in bone growth, repair and disease. Greater understanding of this will provide new ways to treat bone disease. We will also determine if these macrophages help support stem cells that reside near bone surfaces, which may provide new treatment strategies to improve bone marrow transplantation in cancer.