Objective: Develop a non-terminal animal model of acute joint injury that demonstrates clinical and morphological evidence of early post-traumatic osteoarthritis (PTOA). Methods: An osteochondral (OC) fragment was created arthroscopically in one metacarpophalangeal (MCP) joint of 11 horses and the contralateral joint was sham operated. Eleven additional horses served as unoperated controls. Every 2 weeks, force plate analysis, flexion response, joint circumference, and synovial effusion scores were recorded. At weeks 0 and 16, radiographs (all horses) and arthroscopic videos (OC injured and sham joints) were graded. At week 16, synovium and cartilage biopsies were taken arthroscopically from OC injured and sham joints for histologic evaluation and the OC fragment was removed. Results: OC fragments were successfully created and horses were free of clinical lameness after fragment removal. Forelimb gait asymmetry was observed at week 2 (. P = 0.0012), while joint circumference (. P < 0.0001) and effusion scores (. P < 0.0001) were increased in injured limbs compared to baseline from weeks 2 to 16. Positive flexion response of injured limbs was noted at multiple time points. Capsular enthesophytes were seen radiographically in injured limbs. Articular cartilage damage was demonstrated arthroscopically as mild wear-lines and histologically as superficial zone chondrocyte death accompanied by mild proliferation. Synovial hyperemia and fibrosis were present at the site of OC injury. Conclusion: Acute OC injury to the MCP joint resulted in clinical, imaging, and histologic changes in cartilage and synovium characteristic of early PTOA. This model will be useful for defining biomarkers of early osteoarthritis and for monitoring response to therapy and surgery.
Bibliographical noteFunding Information:
The project described was supported in part by Grant Number 1R15AR059612-01 from National Institute of Arthritis and Musculoskeletal and Skin diseases (NIAMS)/National Institutes of Health (NIH) (TNT), and in part by a grant supported by the Agricultural Experiment Station (TNT). Graduate support (MKB) was provided by an NIH/National Center for Research Resources (NCRR) T32 Training Grant ( 1T32RR018719-01 ) in Comparative Medicine and Pathology Training (CSC).
- Animal model