This is ongoing project to define the role and mechanism of endogenous glucocorticoids in osteoarthritis.
Background:Osteoarthritis is one of the most common chronic diseases worldwide. With the rise in life expectancy the prevalence of degenerative joint disease has increased continuously and across all ethnicities. It is estimated that by the age 65 years, 80% of people have radiographic evidence of osteoarthritis. Treatments for osteoarthritis are primarily prescribed to reduce symptoms with no medical interventions known to effectively prevent or delay the development of degenerative joint disease. Intra-articular glucocorticoid injection is one of treatments used for decades for pain relief. Recently, a clinical study report that Intra-articular glucocorticoid injection resulted in significantly greater cartilage volume loss and no significant difference in knee pain when compare to intra-articular saline placebo osteoarthritis group (McAlindon et al., JAMA, 2017). We investigated the impact of endogenous glucocorticoids in a murine model of surgically induced osteoarthritis. We made the observation that the surgically induced osteoarthritis was attenuated when glucocorticoid signalling was disrupted in osteoblasts/osteocytes. The critical role of endogenous glucocorticoids in the pathogenesis of osteoarthritis has never been recognised before. Our findings allow for an innovative approach to a very old but unsolved problem of great medical and social significance. We aim to elucidate how glucocorticoids regulate osteoblast, osteocyte and chondrocyte function to promote the development of degenerative joint damage.
Project hypothesis: Osteoblasts, under the control of endogenous glucocorticoids, play a key role in promote the pathogenesis of osteoarthritis.
1. 1. To identify the cells in bone and cartilage, and the associated molecular signalling pathways that mediate the pro-degenerative actions of endo¬genous glucocorticoids.
2. 2. To determine whether inhibition of intracellular glucocorticoid signalling in osteoblasts, osteocytes and/or chondrocytes can prevent the development or progression of osteoarthritis
The opportunity ID for this research opportunity is 1159