Axial Compressive Loading Attenuates Early Osteoarthritis by Reducing Subchondral Bone Remodeling

作者：Jianqun Wu, Yonghao Pan, Yangyi Yu, Qihao Yang, Qisong Liu, Yang Liu, Jinhao Zhong, Linhao Fu, Haotian Cai, Chao Liu, Guangheng Li · 发表于：The American Journal of Sports Medicine · 年份：2023 · DOI：10.1177/03635465231164644 · 被引用次数：25 · 研究领域：Osteoarthritis Treatment and Mechanisms、Tendon Structure and Treatment、Total Knee Arthroplasty Outcomes

BACKGROUND: Mechanical loading and alendronate (ALN) can be used as noninvasive physical therapy methods for osteoarthritis (OA). However, the timing and efficacy for treatments are unknown. PURPOSE: To determine whether the timing of mechanical loading and ALN influences the pathobiological changes of OA. STUDY DESIGN: Controlled laboratory study. METHODS: Mice with OA induced by anterior cruciate ligament transection were subjected to early (1-3 weeks) or late (5-7 weeks) axial compressive dynamic load or intraperitoneal injection of ALN. Changes in gait were analyzed using gait analysis system, pathobiological changes in subchondral bone, cartilage, osteophyte, and synovitis were assessed using micro-computed tomography, tartrate-resistant acid phosphatase staining, pathologic section staining, and immunohistochemistry at 1, 2, 4, and 8 weeks. RESULTS: At 1, 2, and 4 weeks, the OA limb had lower mean footprint pressure intensity, lower bone volume per tissue volume (BV/TV) in the subchondral bone, and more osteoclasts. At 4 weeks, the early loading, ALN, and load + ALN treatments induced less cartilage destruction, with a corresponding reduction in Osteoarthritis Research Society International score and increased hyaline cartilage thickness. The treatments also resulted in fewer osteoclasts and higher BV/TV and bone mineral density of subchondral bone and suppressed inflammation and interleukin 1β- and tumor necrosis factor α-positive cells in synovium. At 8 weeks, early l...