The First Clinical Medical College, Qingdao University, Qingdao, 266071, China.
Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
J Orthop Surg Res. 2024 Sep 28;19(1):591. doi: 10.1186/s13018-024-05081-4.
Acute cartilage injuries, such as intra-articular fractures and blunt impacts, frequently result in chondrocyte death and extracellular matrix (ECM) degradation, significantly elevating the risk of post-traumatic osteoarthritis (PTOA). Despite advances in treatment, no effective therapies currently exist to fully cure PTOA or halt its progression. This study explores the protective effects of the dietary fatty acid eicosapentaenoic acid (EPA) on human primary chondrocytes (HPCs) and cartilage explants exposed to mechanical overload and blunt trauma. HPCs were isolated and subjected to mechanical stretching using BioFlex six-well culture plates, while cartilage explants were subjected to impact loading via a customized drop tower. EPA was incorporated into the culture medium, followed by assays to evaluate cell viability, calcium (Ca²⁺) influx, apoptosis, reactive oxygen species (ROS) levels, and collagen type II alpha (Col-2a) expression. EPA treatment markedly decreased chondrocyte mechanical sensitivity, as demonstrated by enhanced cell viability and reduced lactate dehydrogenase (LDH) release. Furthermore, EPA inhibited Piezo1 activation, leading to lower intracellular Ca²⁺ concentrations, decreased apoptosis, and diminished ROS levels. In cartilage explants, EPA improved chondrocyte viability, minimized structural damage, and sustained higher Col-2a expression compared to the blunt trauma group. These results indicate that EPA effectively shields chondrocytes and cartilage explants from mechanical overload-induced damage by inhibiting Piezo1 activation and mitigating Ca²⁺ influx, apoptosis, and oxidative stress. The findings suggest that EPA supplementation could offer a promising strategy for preventing PTOA progression following acute cartilage injuries. Further research is warranted to assess the clinical applications of EPA and confirm its efficacy in larger animal models and human trials.
急性软骨损伤，如关节内骨折和钝性撞击，常导致软骨细胞死亡和细胞外基质（ECM）降解，显著增加创伤后骨关节炎（PTOA）的风险。尽管治疗取得了进展，但目前尚无有效的治疗方法可以完全治愈 PTOA 或阻止其进展。本研究探讨了膳食脂肪酸二十碳五烯酸（EPA）对机械过载和钝性创伤下的人原代软骨细胞（HPC）和软骨外植体的保护作用。分离 HPC 并用 BioFlex 六孔培养板进行机械拉伸，同时通过定制落塔对软骨外植体进行冲击加载。将 EPA 掺入培养基中，然后进行细胞活力、钙（Ca²⁺）内流、细胞凋亡、活性氧（ROS）水平和 II 型胶原 α（Col-2a）表达的测定。EPA 处理显著降低了软骨细胞的机械敏感性，表现为细胞活力增强和乳酸脱氢酶（LDH）释放减少。此外，EPA 抑制了 Piezo1 的激活，导致细胞内 Ca²⁺浓度降低、细胞凋亡减少和 ROS 水平降低。在软骨外植体中，与钝性创伤组相比，EPA 提高了软骨细胞的活力，最大限度地减少了结构损伤，并维持了更高的 Col-2a 表达。这些结果表明，EPA 通过抑制 Piezo1 的激活和减轻 Ca²⁺内流、细胞凋亡和氧化应激，有效地保护软骨细胞和软骨外植体免受机械过载诱导的损伤。研究结果表明，EPA 补充可能是预防急性软骨损伤后 PTOA 进展的一种有前途的策略。需要进一步的研究来评估 EPA 的临床应用，并在更大的动物模型和人体试验中确认其疗效。
