Regulation Of Osteoclast Differentiation And Function By The PKC Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$424,189.00
Summary
Developing strategies to control the formation of osteoclasts which underlines many disorders such as osteoporosis and osteoarthritis has been a major focus of bone research.The proposed research examines the fundamental role of Protein Kinase C (PKC) in bone resorption.This work will help elucidate the role of PKC in osteoclast formation;define the physiological role of PKC in bone structure and bone resorption in vivo and develop the treatment of bone disorders.
Interaction Of Rab3D And Tctex-1 Is Required For Bone Resorption Through The Regulation Of Post-TGN Vesicle Trafficking
Funder
National Health and Medical Research Council
Funding Amount
$391,510.00
Summary
Osteoclasts are multinucleated cells responsible for the breakdown-resorption of bone tissue. Elevated osteoclast numbers and-or activities is a major hallmark of a number of debilitating Orthopaedic-related diseases including osteoporosis, arthritis, bone cancer and aseptic loosening. Among these, osteoporosis is endemic in Western society with an estimated 1 in 2 women and 1 in 3 men sustaining a fracture in their lifetime. It is well accepted that the transport of carrier vesicles containing ....Osteoclasts are multinucleated cells responsible for the breakdown-resorption of bone tissue. Elevated osteoclast numbers and-or activities is a major hallmark of a number of debilitating Orthopaedic-related diseases including osteoporosis, arthritis, bone cancer and aseptic loosening. Among these, osteoporosis is endemic in Western society with an estimated 1 in 2 women and 1 in 3 men sustaining a fracture in their lifetime. It is well accepted that the transport of carrier vesicles containing bone destructive enzymes is critical for bone resorption by osteoclasts. Although vesicle transport has been shown to be associated with microtubules (the cells skeleton), the molecular mechanisms responsible for vesicle and microtubule interaction are largely unknown. We have identified a novel interaction between Rab3D, a vesicle transport molecule, with Tctex-1, a microtubule-binding protein. We propose that the binding of Rab3D to Tctex-1 in osteoclasts is essential for the interaction of vesicles with microtubules and, hence, osteoclast function. The focus of this project is to further confirm our hypothesis by analysing the importance of this interaction in osteoclast-mediated bone resorption. The anticpated outcomes of the proposed project are: 1) Rab3D-mediated vesicle transport is directed via the microtubule network; 2) Interaction between Rab3D and Tctex-1 is cruical for the coupling of Rab3D-mediated vesicle transport to the microtubules; and 3)Disruption of the Rab3D-Tctex-1 interaction may impair bone resorption. Understanding the molecular mechanisms which regulate osteoclastic vesicle trafficking might therefore enable us to develop new strategies to specifically target and inhibit breakdown of bone tissue.Read moreRead less
A Randomised Controlled Trial Examining Stability Of New Types Of Highly Porous Surfaced Acetabular Components In Total Hip Replacement
Funder
National Health and Medical Research Council
Funding Amount
$216,490.00
Summary
Numbers of total hip replacements are steadily increasing. The most common complication of hip replacement is late implant loosening, which can be predicted by early migration. We will examine early migration of a trabecular metal acetabular cup without screws, compared to a titanium fibre metal acetabular cup fixed with screws. Ideally, an acetabular cup would achieve a level of initial stability by press-fit alone without screws, as screws increase the risk of bone loss around the prosthesis.
The Interaction Of Ac45 With V-ATPase And Its Function In Osteoclastic Bone Resorption
Funder
National Health and Medical Research Council
Funding Amount
$671,613.00
Summary
Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and increased susceptibility to fractures. Of concern is osteoporotic fractures in the elderly are linked with increased mortality rates. Also, diseases associated with excess bone resorption place significant financial burden on the health care systems. We will examine the role of proton pump in bone resorption as a potential target for the treatment of osteoporosis.
The Role Of CHKB In Osteoclastic Bone Resorption And Bone Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$565,695.00
Summary
Osteoporosis is a devastating disorder. Osteoporotic fractures in the elderly have been correlated with increased mortality rates. Osteoporosis alone costs $13.8 billion p.a. in USA and tens of millions of dollars in Australia. Cost to society of our ageing population for people become disabled by hip fractures alone could triple by the year 2040. Our research examines the role of CHKB in bone loss which may underscore its potential as a new molecular target for anti-resorptive drug development.
The Role Of The Secreted SVS7 Protein In Bone Homeostasis
Funder
National Health and Medical Research Council
Funding Amount
$605,122.00
Summary
Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue leading to bone fragility and an increased susceptibility to fractures caused by imbalance between cells that are constantly reabsorbing and reforming bone. The cost to society with our aging population and individuals who become disabled by hip fractures could triple by the year 2040.The proposed project studies a novel factor that controls bone mass. Its potential is for therapeutic treatment.
Reducing The Burden Of Joint Replacement: An Innovative Biofeedback Device For Post-Surgical Rehabilitation.
Funder
National Health and Medical Research Council
Funding Amount
$169,500.00
Summary
This project aims to develop a robust wearable device capable of providing immediate audible feedback with respect to knee motion for enhanced post-knee replacement surgery rehabilitation, suitable for use by older people both independently and supervised at home or in the clinic. As there is a current unmet need for such wearable biofeedback devices, this project will lead to intellectual property generation, strengthened partnerships between the involved parties and identification of an indust ....This project aims to develop a robust wearable device capable of providing immediate audible feedback with respect to knee motion for enhanced post-knee replacement surgery rehabilitation, suitable for use by older people both independently and supervised at home or in the clinic. As there is a current unmet need for such wearable biofeedback devices, this project will lead to intellectual property generation, strengthened partnerships between the involved parties and identification of an industry partner to commercialise the technology.Read moreRead less
Regulation Of Key Pathways Causing Peri-implant Bone Loss.
Funder
National Health and Medical Research Council
Funding Amount
$403,639.00
Summary
The failure of bone prostheses is becoming a major health problem in our aging population. Despite the impressive success of joint replacement surgery, a significant number of arthroplasties fail. It is now apparent that most implants fail due to bone loss around them which leads to loosening. This project aims to obtain a better understanding of the causes of implant failure and find ways to extend the life of these implants .
Improving The Functional Outcomes Of Lower Limb Orthopaedic Surgery
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
While orthopaedic surgery usually achieves pain relief and improves function somewhat, it can often leave a patient unable to perform certain activities. And these abnormal movement patterns are likely to cause further problems. This project will objectively measure post-surgical function, in order to improve the surgery and rehabilitation of some of the most complex orthopaedic conditions. The goal is that patients receive the maximum benefit from surgery.