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

Abstract

Objective: 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 in vivo cyclic tibial compression. We hypothesized that low-level cyclic compression would attenuate post-traumatic OA symptoms induced by destabilization of the medial meniscus (DMM). Methods: 10-week-old C57Bl/6J male mice underwent DMM surgery (n ¼ 51). After a 5-day postoperative 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. Results: Compared to DMM alone, low-level cyclic compression for 6 weeks attenuated DMM-induced cartilage degradation (OARSI score, P ¼ 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 ¼ 0.033, 95% CI: 3.27e114.45 mm), and moderate loading attenuated subchondral bone sclerosis after 6 weeks (tissue mineral density (TMD), P ¼ 0.011, 95% CI: 6.32e70.60 mg HA/ccm) compared to limbs that only underwent DMM. Finally, loading had subtle beneficial effects on cartilage cellularity and aggrecanase activity after DMM. Conclusion: 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.

Early inhibition of subchondral bone remodeling slows load-induced posttraumatic osteoarthritis development in mice

“…Several factors may contribute to increased damage severity following a single load compared to daily loading, in particular reduced joint range of motion over time in the single‐load model with the development of ligament calcifications that do not form with daily loading, perhaps due to daily loading maintaining range of motion within the joint. The roles of daily cage activity, repeated exposure to anesthesia, daily injections, and potential protective effects of daily loading ( 53 ) in relation to OA development and progression need to be investigated further to better understand the difference between these two load‐induced preclinical OA models.…”

Low-Intensity Pulsed Ultrasound Alleviates Hypoxia-Induced Chondrocyte Damage in Temporomandibular Disorders by Modulating the Hypoxia-Inducible Factor Pathway

“…TMDs have a complex and multifactorial etiology (Florjanski et al, 2019). Mechanical loading has been shown to contribute to their onset and progression (Holyoak et al, 2019), and metabolismrelated dysbiosis and the accumulation of inflammatory cytokines might also be involved in disease pathogenesis (Wadhwa and Kapila, 2008;Park and Chung, 2016). However, the precise mechanisms underlying TMDs remain unclear.…”

Exercise for Osteoarthritis: A Literature Review of Pathology and Mechanism

“…For example, a daily external force has been used to compress OA mice under low or medium intensity, and the pathological changes of articular cartilage were observed in the second and sixth weeks. Moreover, low- and medium-intensity compression can reduce the degeneration of articular cartilage and osteophytes of subchondral bone in mice and is very beneficial to the damaged joints, making it an effective method for the treatment of OA ( Holyoak et al, 2019 ).…”