Objective

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.

Design

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.

Results

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).

Conclusions

These data suggest that early unloading following joint injury can reduce inflammation and potentially slow PTOA progression.

中文翻译：

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小鼠的早期机械卸载和抗炎治疗减少了创伤后骨关节炎的进展

客观的

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，但这些早期干预如何影响 PTOA 进展尚不清楚。我们假设早期卸载和抗炎治疗会减少关节炎症并减缓 PTOA 进展。

设计

小鼠因非侵入性 ACL 断裂而受伤，随后进行后肢卸载 (HLU) 或正常笼活动（地面控制：GC）7 天，之后所有小鼠都可以进行正常的笼活动。HLU 和 GC 小鼠每天用塞来昔布（CXB；10 mg/kg IP）或载体治疗。在受伤后 7、14、21 和 28 天，使用体内荧光成像评估蛋白酶活性，使用微型计算机断层扫描量化骨赘形成和骨骺骨小梁，并使用全关节组织学评估滑膜炎和关节软骨。

结果

HLU 在受伤后第 7 天（卸载期间）显着降低蛋白酶活性（-22-30% 与 GC 相比）和滑膜炎（-24-50% 与 GC 相比），但这些差异在以后的时间点没有保持。同样，HLU 小鼠的骨小梁体积在卸载期间部分保留（HLU 小鼠为 -14-15% BV/TV，相对于未受伤的 GC 小鼠为 -21-22%），但这些差异在重新加载期间没有保持。HLU 和 CXB 均减少了骨赘体积，但这些处理没有累加效应（HLU：-46%，CXB：-30%，HLU + CXB：-35%，相对于第 28 天的载体 GC）。

结论

这些数据表明，关节损伤后的早期卸载可以减少炎症并可能减缓 PTOA 进展。