2015 ISAKOS Biennial Congress ePoster #315

Joint Instability Induces an Inflammatory Response in a Rabbit Knee Model

Christian Egloff, MD, Basel, Basel SWITZERLAND
Andrew Sawatsky, Msc, Calgary, Alberta CANADA
Timothy Leonard, PhD, Calgary CANADA
Victor Valderrabano, MD, PhD, Basel SWITZERLAND
David A. Hart, PhD, Calgary, Alberta CANADA
Walter Herzog, Prof., Calgary, Alberta CANADA
University of Calgary, Calgary, Alberta, CANADA

FDA Status Not Applicable

Summary: Joint instability in a muscle paralysis model leads to expression of proinflammatory, degradative proteinases of the intraarticular structures in the intact knee joint.

Abstract:

Introduction

Joint instability is considered to promote early osteoarthritic changes in the knee. Also inflammatory reactions are associated with cartilage degradation in osteoarthritis. Therefore, the goal of the present study was to investigate the in vivo effects of joint instability on the expression of proinflammatory proteinases implicated in OA in an otherwise intact rabbit knee joint model.

Methods

10 1-year-old female New Zealand White rabbits (average 5.7kg, range 4.8-6.6kg) were randomly assigned to receive unilateral intramuscular injection of Botulinum toxin A (BTX-A, n=5) termed “instability group” or no treatment (n=5), termed control group. This resulted in three groups for analysis: normal knees from the control group, experimentally treated knees from the instability group, and contralateral, untreated knees from the instability group. After ninety days, synovial tissue, collateral ligaments and menisci from both compartments of all knees were collected and analyzed for specific mRNA levels using RT-PCR. mRNA levels were compared across groups using multivariate linear regression with adjustment for tissue type and compartment.

Results

The analysis of the synovial tissue showed significant elevation of mRNA levels of collagen I (p=0.002), collagen III (p=0.022) and INOS (p=0.013), TGF-B (p=0.001), IL-1 (p=0.038) and IL-6 (p=0.027) compared to the healthy controls. Borderline significance showed COX-2 (p=0.065).
The posthoc analysis showed a significantly higher expression of these markers in the medial compared to the lateral meniscus (p<0.001). The collateral ligaments showed no consistent changes compared to the control animals.

Conclusion

Joint instability in a muscle paralysis model leads to expression of proinflammatory, degradative proteinases of the synovial tissue in the otherwise intact knee joint. This result is surprising and adds to the literature the idea that joint instability caused by muscle paralysis may promote an inflammatory intraarticular milieu, which may contribute to the development of early stages of OA.