University of California Davis Health, Department of Orthopaedic Surgery, Lawrence J. Ellison Musculoskeletal Research Center, 4635 2nd Ave, Suite 2000, Sacramento, CA 95817, USA.
Lawrence Livermore National Laboratory, Physical and Life Sciences Directorate, 7000 East Avenue, L-452, Livermore, CA 94550, USA.
Osteoarthritis Cartilage. 2021 Dec;29(12):1709-1719. doi: 10.1016/j.joca.2021.09.014. Epub 2021 Oct 13.
Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease initiated by injury. Early phase (0-7 days) treatments often include rest (unloading) and anti-inflammatory medications, but how those early interventions impact PTOA progression is unknown. We hypothesized that early unloading and anti-inflammatory treatment would diminish joint inflammation and slow PTOA progression.
Mice were injured with non-invasive ACL rupture followed by hindlimb unloading (HLU) or normal cage activity (ground control: GC) for 7 days, after which all mice were allowed normal cage activity. HLU and GC mice were treated with daily celecoxib (CXB; 10 mg/kg IP) or vehicle. Protease activity was evaluated using in vivo fluorescence imaging, osteophyte formation and epiphyseal trabecular bone were quantified using micro-computed tomography, and synovitis and articular cartilage were evaluated using whole-joint histology at 7, 14, 21, and 28 days post-injury.
HLU significantly reduced protease activity (-22-30% compared to GC) and synovitis (-24-50% relative to GC) at day 7 post-injury (during unloading), but these differences were not maintained at later timepoints. Similarly, trabecular bone volume was partially preserved in HLU mice at during unloading (-14-15% BV/TV for HLU mice, -21-22% for GC mice relative to uninjured), but these differences were not maintained during reloading. Osteophyte volume was reduced by both HLU and CXB, but there was not an additive effect of these treatments (HLU: -46%, CXB: -30%, HLU + CXB: -35% relative to vehicle GC at day 28).
These data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.
创伤后骨关节炎（PTOA）是一种由损伤引发的退行性关节疾病。早期（0-7 天）治疗通常包括休息（卸载）和抗炎药物，但这些早期干预措施如何影响 PTOA 进展尚不清楚。我们假设早期卸载和抗炎治疗将减轻关节炎症并减缓 PTOA 进展。
通过非侵入性 ACL 破裂使小鼠受伤，然后进行下肢卸载（HLU）或正常笼活动（地面对照：GC）7 天，之后所有小鼠均允许进行正常笼活动。HLU 和 GC 小鼠每天接受塞来昔布（CXB；10mg/kg IP）或载体治疗。使用体内荧光成像评估蛋白酶活性，使用微计算机断层扫描定量评估骨赘形成和骺板小梁骨，使用全关节组织学评估滑膜炎和关节软骨在损伤后 7、14、21 和 28 天。
HLU 在受伤后 7 天（卸载期间）显著降低了蛋白酶活性（与 GC 相比降低了 22-30%）和滑膜炎（与 GC 相比降低了 24-50%），但这些差异在后期时间点并未维持。同样，在卸载期间，HLU 小鼠的小梁骨体积也部分得到保留（HLU 小鼠的 BV/TV 减少 14-15%，GC 小鼠减少 21-22%，与未受伤的小鼠相比），但在重新加载期间，这些差异并未维持。骨赘体积减少了 HLU 和 CXB，但这些治疗方法没有叠加效应（HLU：-46%，CXB：-30%，HLU+CXB：与载药 GC 相比，第 28 天减少 35%）。
这些数据表明，关节损伤后早期卸载可以减轻炎症并可能减缓 PTOA 进展。
