Early Intervention with Cdk9 Inhibitors to Prevent Post-Traumatic Osteoarthritis
Technical Report,30 Sep 2014,29 Sep 2015
University of California, Davis Davis United States
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We proposed to test in aim 1 whether inhibition of Cdk9 would reduce the early transcriptional response to joint injury, and in aim 2 whether this would delay or prevent the subsequent development of post-traumatic osteoarthritis. In the first progress report, we made significant progress on Aim 1, essentially demonstrating that Cdk9 inhibitors reduce early transcriptional responses to joint injury using in-vitro and in-vivo models. In this progress report, we made substantial progress in Aim2, demonstrating that prevention of early transcriptional response to joint injury reduces many of the early signs of osteoarthritis initiation and progression. We show this both in-vitro using cartilage explants, and in-vivo in our mouse model of ACL-rupture PTOA. In-vitro, using explant cartilage subjected to impact injury, Cdk9 inhibitors prevent mechanical injury-induced inflammation, apoptosis and matrix degradation. In-vivo, Cdk9 inhibitors reduce inflammation, synovitis, fibrosis, loss of cartilage mechanical properties, loss of subchondral bone, and osteophyte formation.
- Anatomy and Physiology
- Medicine and Medical Research