Early Intervention with Cdk9 Inhibitors to Prevent Post-Traumatic Osteoarthritis
Abstract
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. We made significant progress on aim 1 during the past 18 months. The first manuscript describing the in-vitro results on the chondroprotective effects of Cdk9 inhibitors is published in Arthritis&Rheumatology. We next began testing whether inhibition of Cdk9 in mouse knees protects against the acute inflammatory response at early times post-injury. At first we tested the transcription of early response genes since that process is directly controlled by Cdk9. These tests were very successful: a single intraperitoneal injection of Cdk9 inhibitor significantly reduced the acute response, and multiple injections reduced the acute response to baseline levels. Next, we looked at proteinase activity within the joints, which is initiated by the acute response and is responsible for cartilage degeneration. These tests were also successful. We are currently following through with additional analyses including in-vivo imaging and cytokine profiling as described in the proposal. This will be the material for our second manuscript, which we also expect to submit to Arthritis&Rheumatology. Given these positive results during the acute phase, we are well-positioned to initiate the longer-term studies we proposed in aim 2 in the near future.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA607959
Entities
People
- Dominik R Haudenschild
Organizations
- University of California