Low-level cyclic tibial compression attenuates early osteoarthritis progression after joint injury in mice

Abstract

Mechanical loading and joint health have a unique relationship in osteoarthritis (OA) onset and progression. Although high load levels adversely affect cartilage health, exercise that involves low to moderate load levels can alleviate OA symptoms. We sought to isolate the beneficial effects of mechanical loading using controlled invivo cyclic tibial compression. We hypothesized that low-level cyclic compression would attenuate post-traumatic OA symptoms induced by destabilization of the medial meniscus (DMM). 10-week-old C57Bl/6J male mice underwent DMM surgery (n=51). After a 5-day post-operative recovery period, we applied daily cyclic tibial compression to the operated limbs at low (1.0N or 2.0N) or moderate (4.5N) magnitudes for 2 or 6 weeks. At the completion of loading, we compared cartilage and peri-articular bone features of mice that underwent DMM and loading to mice that only underwent DMM. Compared to DMM alone, low-level cyclic compression for 6 weeks attenuated DMM-induced cartilage degradation (OARSI score, P=0.008, 95% confidence interval (CI): 0.093 to 0.949). Low-level loading attenuated DMM-induced osteophyte formation after 2 weeks (osteophyte size, P=0.033, 95% CI: 3.27-114.45μm), and moderate loading attenuated subchondral bone sclerosis after 6 weeks (tissue mineral density (TMD), P=0.011, 95% CI: 6.32-70.60mg HA/ccm) compared to limbs that only underwent DMM. Finally, loading had subtle beneficial effects on cartilage cellularity and aggrecanase activity after DMM. Low-level cyclic compression is beneficial to joint health after an injury. Therefore, the progression of early OA may be attenuated by applying well controlled, low-level loading shortly following joint trauma.