Institute of Life Course and Medical Sciences, University of Liverpool, Apex building, West Derby street, Liverpool, L7 8TX, UK.
School of Engineering, University of Liverpool, Brownlow Hill, Liverpool, L69 3GH, UK.
Arthritis Res Ther. 2022 May 30;24(1):128. doi: 10.1186/s13075-022-02798-7.
Knee joint injuries, common in athletes, have a high risk of developing post-traumatic osteoarthritis (PTOA). Ligaments, matrix-rich connective tissues, play important mechanical functions stabilising the knee joint, and yet their role post-trauma is not understood. Recent studies have shown that ligament extracellular matrix structure is compromised in the early stages of spontaneous osteoarthritis (OA) and PTOA, but it remains unclear how ligament matrix pathology affects ligament mechanical function. In this study, we aim to investigate both structural and mechanical changes in the anterior cruciate ligament (ACL) in a mouse model of knee trauma.
Knee joints were analysed following non-invasive mechanical loading in male C57BL/6 J mice (10-week-old). Knee joints were analysed for joint space mineralisation to evaluate OA progression, and the ACLs were assessed with histology and mechanical testing.
Joints with PTOA had a 33-46% increase in joint space mineralisation, indicating OA progression. Post-trauma ACLs exhibited extracellular matrix modifications, including COL2 and proteoglycan deposition. Additional changes included cells expressing chondrogenic markers (SOX9 and RUNX2) expanding from the ACL tibial enthesis to the mid-substance. Viscoelastic and mechanical changes in the ACLs from post-trauma knee joints included a 20-21% decrease in tangent modulus at 2 MPa of stress, a decrease in strain rate sensitivity at higher strain rates and an increase in relaxation during stress-relaxation, but no changes to hysteresis and ultimate load to failure were observed.
These results demonstrate that ACL pathology and viscoelastic function are compromised in the post-trauma knee joint and reveal an important role of viscoelastic mechanical properties for ligament and potentially knee joint health.
膝关节损伤在运动员中很常见，患创伤后骨关节炎（PTOA）的风险很高。韧带是富含基质的结缔组织，对稳定膝关节具有重要的机械功能，但它们在创伤后的作用尚不清楚。最近的研究表明，韧带细胞外基质结构在自发性骨关节炎（OA）和 PTOA 的早期阶段受损，但尚不清楚韧带基质病理学如何影响韧带的机械功能。在这项研究中，我们旨在研究膝关节创伤小鼠模型中前交叉韧带（ACL）的结构和力学变化。
对雄性 C57BL/6J 小鼠（10 周龄）进行非侵入性机械加载后，分析膝关节。通过关节间隙矿化评估 OA 进展，并用组织学和力学测试评估 ACL。
患有 PTOA 的关节关节间隙矿化增加 33-46%，表明 OA 进展。创伤后的 ACL 表现出细胞外基质的改变，包括 COL2 和蛋白聚糖的沉积。其他变化包括表达软骨形成标志物（SOX9 和 RUNX2）的细胞从 ACL 胫骨附着点扩展到中体。来自创伤后膝关节的 ACL 的粘弹性和机械变化包括在 2 MPa 应力下切线模量降低 20-21%，在较高应变率下应变率敏感性降低，以及在应力松弛期间松弛增加，但没有观察到滞后和最终破坏载荷的变化。
这些结果表明，ACL 病理学和粘弹性功能在创伤后膝关节中受损，并揭示了粘弹性力学特性对韧带和潜在膝关节健康的重要作用。
