Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, Ulm 89081, Germany.
Department of Orthopedics, University of Ulm, Ulm 89081, Germany.
Int J Mol Sci. 2019 Jun 14;20(12):2916. doi: 10.3390/ijms20122916.
Joint injuries are highly associated with the development of post-traumatic osteoarthritis. Previous studies revealed cell- and matrix-protective effects of N-acetylcysteine (NAC) after ex vivo cartilage trauma, while chondroanabolic stimulation with bone morphogenetic protein 7 (BMP7) enhanced type II collagen (COL2) expression. Here, as a next step, we investigated the combined and individual efficacy of intra-articular antioxidative and chondroanabolic treatment in a rabbit in vivo cartilage trauma model. Animals were randomly divided into group A (right joint: trauma (T); left joint: T+BMP7) and group B (right joint: T+NAC; left joint: T+BMP7+NAC). Condyles were impacted with the use of a spring-loaded impact device to ensure defined, single trauma administration. After 12 weeks, histopathological analysis was performed and the presence of matrix metalloproteinase 13 (MMP-13) and COL2 was assessed. Trauma-induced hypocellularity, MMP-13 expression, and cell cluster formation were reduced in NAC-treated animals. In contrast, BMP7 further increased cluster formation. Moreover, synovial concentrations of COL2 carboxy propeptide (CPII) and proteoglycan staining intensities were enhanced in NAC- and NAC+BMP7-treated joints. For the first time, the efficacy of NAC regarding early harm reduction after blunt cartilage trauma was demonstrated in vivo. However, parallel administration of BMP7 was not significantly superior compared to NAC alone.
关节损伤与创伤后骨关节炎的发生高度相关。先前的研究表明，N-乙酰半胱氨酸（NAC）在离体软骨损伤后具有细胞和基质保护作用，而骨形态发生蛋白 7（BMP7）的软骨合成刺激作用则增强了 II 型胶原（COL2）的表达。在此，作为下一步，我们在兔体内软骨损伤模型中研究了关节内抗氧化和软骨合成治疗的联合和单独疗效。动物随机分为 A 组（右膝关节：创伤（T）；左膝关节：T+BMP7）和 B 组（右膝关节：T+NAC；左膝关节：T+BMP7+NAC）。使用弹簧加载冲击装置撞击髁，以确保进行定义的单次创伤给药。12 周后，进行组织病理学分析，并评估基质金属蛋白酶 13（MMP-13）和 COL2 的存在。在 NAC 处理的动物中，创伤引起的细胞减少、MMP-13 表达和细胞簇形成减少。相比之下，BMP7 进一步增加了簇形成。此外，NAC 和 NAC+BMP7 治疗关节中的滑液 COL2 羧基前肽（CPII）和蛋白聚糖染色强度增加。这是首次在体内证明 NAC 对钝性软骨损伤后早期减轻伤害的疗效。然而，与单独使用 NAC 相比，平行给予 BMP7 并没有显著优势。
