Prof Jiake XU
|Recipient:||Prof Jiake XU|
|Intended department:||University of Western Australia – School of Pathology and Laboratory Medicine- Funded by the Estate of the late Heather Joy McKenzie|
|Molecular Mechanisms and Therapeutic Effects of Carnosol on Collagen-induced Arthritis and osteolysis
Arthritis is a systemic inflammation that affects millions of people, causing joint pain and deformity. Pathological bone destruction by osteoclasts, cells that take away bone is a characteristic feature of rheumatoid arthritis. Drugs that inhibit bone destruction are critically needed for the prevention and treatment of bone loss by osteoclasts. Although there has been some success in conventional pharmacological treatment of arthritis, with the use of analgesics, steroids, non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), there is a growing trend of arthritis patients using complementary and alternative medicine. Accumulating evidence indicates the great potential of natural compounds for the treatment of arthritis conditions. The popularity of using natural compounds in arthritis treatment is ever increasing, thus it is important to study natural compounds to provide professional advice to the public. However, evidence of the effectiveness and mechanisms of actions of these therapies in the treatment of arthritis remains lacking. Importantly, we have pursued laboratory investigations of naturally occurring compounds that demonstrate in vitro activity. Over the past several years, we have developed assays and protocols that enable efficient and high through put in-vitro screening of natural compounds for the inhibition of bone resorbing osteoclasts, a key therapeutic target for the treatment of osteolytic bone diseases. Previous work has shown that natural compounds, including parthenolide, mangiferin, and honeybee propolis inhibit osteoclast formation, bone resorption and RANKL-induced NF-kB activity. This work has been undertaken in anticipation of potential clinical development and application. The use of complementary medicines for bone and joint health requires very high levels of safety and efficacy, as well as evidence-based practice.
Pathological bone destruction by the osteoclast is a characteristic of many bone diseases such as rheumatoid arthritis, osteomyelitis, septic arthritis and periodontitis-related bone loss. Arthritis is a major cause of disability and chronic pain in Australia, with rheumatoid arthritis affecting around 400,000 Australians. Excessive osteoclastic bone resorption is a hallmark of RA. The economic cost of this condition extends beyond the cost of healthcare, with only 31% of affected individuals able to participate in full time employment compared to 53% of the general population. Drugs that inhibit osteolysis are critically needed for the prevention and treatment of bone loss by osteoclasts. Development of strategies to control the formation or activities of osteoclasts has been a major focus of research into the suppression of osteolysis. The proposed research explores the potential use of natural compound Carnosol for the suppression of osteoclastogenesis, and their potential as treatments for inflammation and infection related bone loss diseases. The outcomes of this work has therefore helped us to: 1) Understand the mechanisms of action of Carnosol, as a prototype compound inhibitor for osteoclast inhibition and bone resorption. 2) Provide essential pre-clinical information on Carnosol for the treatment of RA and pathological osteolysis.
Future research direction: We intend to apply for NHMRC and other commercial funding agents to further carry out this study for human study.
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