Department of Joint and Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China; Department of Orthopedics, Southern University of Science and Technology Hospital, Shenzhen, Guangdong, PR China; Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.
Int J Biol Macromol. 2022 Nov 1;220:1104-1113. doi: 10.1016/j.ijbiomac.2022.08.071. Epub 2022 Aug 18.
The alteration of the extracellular matrix (ECM) homeostasis plays an important role in the development of osteoarthritis (OA). The pathological changes of OA are mainly manifested in the large reduction of components in ECM, like type II collagen and aggrecan, especially hyaluronic acid and chondroitin sulfate and often accompanied by inflammation. Rebuilding ECM and inhibiting inflammation may reverse OA progression. In this work, we developed new magnesium-containing glycosaminoglycans (Mg-GAGs), to create a positive ECM condition for promoting cartilage regeneration and alleviating OA. In vitro results suggested that the introduction of Mg-GAGs contributed to promoting chondrocyte proliferation and facilitated upregulating chondrogenic genes and suppressed inflammation-related factors. Moreover, Mg-GAGs exhibited positive effects on suppressing synovial inflammation, reducing chondrocyte apoptosis and preserving the subchondral bone in the ACLT-induced OA rabbit model. This study provides new insight into ECM-based therapeutic strategy and opens a new avenue for the development of novel OA treatment.
细胞外基质 (ECM) 稳态的改变在骨关节炎 (OA) 的发展中起着重要作用。OA 的病变主要表现为 ECM 成分大量减少，如 II 型胶原和聚集蛋白聚糖，特别是透明质酸和硫酸软骨素，常伴有炎症。重建 ECM 和抑制炎症可能逆转 OA 的进展。在这项工作中，我们开发了新的含镁糖胺聚糖 (Mg-GAGs)，为促进软骨再生和缓解 OA 创造了积极的 ECM 条件。体外结果表明，Mg-GAGs 的引入有助于促进软骨细胞增殖，并有利于上调软骨形成基因和抑制炎症相关因子。此外，Mg-GAGs 对抑制滑膜炎症、减少软骨细胞凋亡和保护 ACLT 诱导的 OA 兔模型中的软骨下骨具有积极作用。本研究为基于 ECM 的治疗策略提供了新的见解，并为新型 OA 治疗的发展开辟了新途径。
