Pilon Fractures: An Ideal Model to Understand Biological Factors Implicated in the Pathogenesis of Post-traumatic Osteoarthritis

  • Aneja, Arun (PI)
  • Landy, David (CoI)
  • McCarthy, John (CoI)
  • Srinath, Arjun (CoI)

Grants and Contracts Details


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).
Effective start/end date5/1/2311/1/23


  • American Orthopaedic Foot and Ankle Society: $49,991.00


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