Mild treadmill exercise inhibits cartilage degeneration via macrophages in an osteoarthritis mouse model

Yuichiro Oka; Kenji Murata; Kaichi Ozone; Yuki Minegishi; Takuma Kano; Naoki Shimada; Naohiko Kanemura

doi:10.1016/j.ocarto.2023.100359

Mild treadmill exercise inhibits cartilage degeneration via macrophages in an osteoarthritis mouse model

Osteoarthr Cartil Open. 2023 Apr 8;5(2):100359. doi: 10.1016/j.ocarto.2023.100359. eCollection 2023 Jun.

Authors

Yuichiro Oka^{1

2}, Kenji Murata³, Kaichi Ozone¹, Yuki Minegishi¹, Takuma Kano¹, Naoki Shimada¹, Naohiko Kanemura³

Affiliations

¹ Department of Health and Social Services, Graduate School of Saitama Prefectural University, Koshigaya, Saitama, Japan.
² Department of Rehabilitation Science, Faculty of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo 060-0812, Japan.
³ Department of Physical Therapy, Health and Social Services, Saitama Prefectural University, Koshigaya, Saitama, Japan.

Abstract

Objective: We previously reported how treadmill exercise can suppress cartilage degeneration. Here, we examined the changes in macrophage dynamics in knee osteoarthritis (OA) during treadmill exercise and the effect of macrophage depletion.

Design: OA mouse model, generated via anterior cruciate ligament transection (ACLT), was subjected to treadmill exercise of different intensities to investigate the effects on cartilage and synovium. In addition, clodronate liposomes, which deplete macrophages, were injected intra-articularly into the joint to examine the role of macrophages during treadmill exercise.

Results: Cartilage degeneration was delayed by mild exercise, and concomitantly, an increase in anti-inflammatory factors in the synovium was observed, with a decrease in the M1 and increase in M2 macrophage ratio. On the contrary, high-intensity exercise led to the progress of cartilage degeneration and was associated with an increase in the M1 and a decrease in the M2 macrophage ratio. The clodronate liposome-induced reduction of synovial macrophages delayed cartilage degeneration. This phenotype was reversed by simultaneous treadmill exercise.

Conclusions: Treadmill exercise, especially at high intensity, was detrimental to articular cartilage, whereas mild exercise reduced cartilage degeneration. Moreover, M2 macrophage response appeared necessary for the chondroprotective effect of treadmill exercise. This study indicates the importance of a more comprehensive analysis of the effects of treadmill exercise, not limited to the mechanical stress added directly to cartilage. Hence, our findings might help determine the type and intensity of prescribed exercise therapy for patients with knee OA.

Keywords: Articular cartilage; Exercise; Inflammation; Macrophage; Osteoarthritis.