Abstract
Summary Statement
We observed that severe muscle weakness leads to OA, whereas a transient inflammatory stimulus did not have a significant effect on cartilage degradation. This arises the thought that a severe but transient inflammation may not be an independent risk factor for OA.
Introduction
Biomechanical disturbances and joint inflammation are known risk factors, which may provoke or advance osteoarthritis (OA). However, the effect of interactions of such risk factors on the onset and progression of OA are still poorly understood. Therefore, the goal of this study was to investigate the in vivo effects of muscle weakness, joint inflammation, and the combination of these two risk factors, on the onset and progression of OA in the rabbit knee.
Patients & Methods
Thirty 1-year-old skeletally mature female New Zealand White rabbits (weight: average 5.7kg, range 4.8–6.6kg) were used in this study. The animals were divided into four experimental groups: (i) surgical transection of the nerve branch of the common femoral nerve leading to the vastus lateralis muscle; (ii) muscle weakness of the quadriceps muscle induced by a chronic intramuscular injection of Botulinum toxin A (BTX-A) (3); (iii) intraarticular injection in the experimental knee joint with commercially available sterile Carrageenan solution to induce a transient severe inflammatory reaction (4); (iv) administration of both intraarticular injection of Carrageenan and intramuscular injection of BTX-A. In each animal, one hind limb was randomly assigned to the experimental intervention, while the contralateral side acted as its own control. Ninety days following intervention, muscle mass, joint diameter and cartilage histology of the femur, femoral groove, tibia and patella were assessed and microscopically analyzed using the OARSI histology score.
Results
Transection of the femoral branch leading to the vastus lateralis as well as the administration of BTX-A led to a significant muscle mass loss for the vastus lateralis and the total quadriceps group, respectively. Similar results were seen in the combined Carrageenan/BTX-A group. There were no changes in total quadriceps muscle mass in the Carrageenan group. Knee joint diameters of the experimental limb were significantly increased in the Carrageenan and Carrageenan/BTX groups. VL transection and BTX-A injection did not cause significant increases in joint diameter. Histologic assessment of the cartilage showed that weakness of the vastus lateralis resulted in significantly higher OARSI scores in the patella and femoral groove, but not the tibiofemoral articulation. The administration of BTX-A caused significant cartilage damage in all 4 compartments (patella, femur, tibia, femoral groove). Intraarticular injection of Carrageenan did not cause significant cartilage damage in any compartment compared to the contralateral side. The combination of BTX-A and Carrageenan resulted in severe cartilage damage in the patella in all four compartments of the knee. The most severe damage was found on the medial side of the tibiofemoral joint and the lateral side of the patellofemoral joint.
Conclusion
Severe muscle weakness over a three months period leads to the onset and progression of OA in the rabbit knee. A transient local inflammatory stimulus did not promote cartilage degradation, nor did it enhance cartilage degradation when it was combined with muscle weakness. This result is surprising and adds to the literature the idea that a severe but transient inflammation may not be an independent risk factor for OA.
