Grants and Contracts Details
Description
Intraarticular pilon fractures have an alarmingly high rate of post-traumatic osteoarthritis
(PTOA) despite anatomic reduction of the articular surface. Elevated synovial inflammatory
proteins triggered by articular injury contribute to PTOA development as they cause chondrocyte
death and extracellular matrix (ECM) degradation. While evidence shows a direct correlation
between concentration of various proinflammatory biomarkers and severity of PTOA, animal
and clinical studies have demonstrated that the post-injury inflammatory response is modifiable.
Levels of various microRNAs (miRNA), regulators of gene expression, are dysregulated in the
cartilage of osteoarthritic (OA) joints and their modulation could deter cartilage and ECM
destruction. Although, miRNAs have been implicated in OA disease progression in animal
models, they have neither been examined in ankle PTOA nor in clinical in-vivo studies. One
potential candidate miRNA, miR-146a, is associated with normal cartilage development and
prevents overexpression of various pro-inflammatory cytokines in degenerative OA. It is
stimulated by physiologic articular cartilage loading and inhibited by supra-physiologic
overloading. This study will test the following hypothesis, intra-articular tibial pilon fractures
decrease miR-146a expression within synovial fluid, thereby up-regulating inflammatory
cytokines that promote PTOA. Synovial fluid from the injured and uninjured ankle of human
subjects taken during the 2-stage repair process will be analyzed for miR-146a levels and
inflammatory protein concentrations. Correlation analysis will examine the relationships
between miR-146a and inflammatory biomarkers during treatment (Aim 1). At two-year post
definitive fixation, the association between miR-146a and inflammatory proteins with
radiographic outcome scores of PTOA severity will be examined (Aim 2).
Status | Finished |
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Effective start/end date | 5/1/23 → 11/1/23 |
Funding
- American Orthopaedic Foot and Ankle Society: $49,991.00
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