Su Weixian, Nie Yupeng, Zheng Shicong, Yao Yongchang
Department of Joint Surgery, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Guangdong Key Laboratory of Orthopaedic Technology and Implant Materials, Guangzhou Medical University, Guangzhou, China.
Biotechnol Bioeng. 2025 Apr;122(4):749-760. doi: 10.1002/bit.28915. Epub 2024 Dec 24.
Chondrocytes maintain the balance of the extracellular matrix by synthesizing glycoproteins, collagen, proteoglycans and hyaluronic acid. Chondrocyte dedifferentiation refers to a process in which chondrocytes lose their mature differentiated phenotype and transform into a fibroblast-like morphology with fewer differentiated stages and inferior function under external stimulation. The important mechanism of homeostasis loss in osteoarthritis (OA) is a change in the chondrocyte phenotype. The dedifferentiation markers of chondrocytes are upregulated in OA, and the pathogenic factors related to OA have also been shown to enhance chondrocyte dedifferentiation. In this review, we compile recent studies on chondrocyte dedifferentiation, with an emphasis on potential markers and the underlying mechanisms of dedifferentiation, as well as the current research progress in inhibiting dedifferentiation or achieving redifferentiation. A deep understanding of chondrocyte dedifferentiation would not only support the pathogenesis of OA theoretically but also provide insightful ideas for regenerative medicine to manipulate the functional phenotype of cells.
软骨细胞通过合成糖蛋白、胶原蛋白、蛋白聚糖和透明质酸来维持细胞外基质的平衡。软骨细胞去分化是指软骨细胞在外部刺激下失去其成熟的分化表型，并转变为成纤维细胞样形态，分化阶段减少且功能较差的过程。骨关节炎（OA）中稳态丧失的重要机制是软骨细胞表型的改变。OA中软骨细胞的去分化标志物上调，并且与OA相关的致病因素也已显示出可增强软骨细胞去分化。在本综述中，我们汇总了关于软骨细胞去分化的最新研究，重点关注潜在标志物和去分化的潜在机制，以及抑制去分化或实现再分化的当前研究进展。深入了解软骨细胞去分化不仅将在理论上支持OA的发病机制，还将为再生医学操纵细胞功能表型提供有见地的想法。
