同济大学岳锐小组的一项最新研究认为Procr⁺软骨祖细胞感知机械刺激来控制关节软骨的维持和再生。2025年7月21日出版的《细胞》发表了这项成果。

该团队在胫骨关节软骨和半月板的浅层发现了罕见的Procr⁺细胞，这些细胞不断补充出生后膝关节的软骨细胞。强迫跑步的机械刺激显著增加了Procr⁺细胞的频率，而尾巴下垂的机械卸载则表现出相反的效果。骨关节炎（OA）激活Procr⁺细胞修复软骨侵蚀，而Procr⁺细胞的基因消融加速了OA的进展。药理或遗传抑制力学传感器Piezo1显著减弱Procr⁺细胞的软骨再生并加重OA。相反，关节内注射Piezo1激动剂可改善OA症状。纯化的小鼠或人Procr⁺表面层细胞经扩张和体内移植后，可自动修复关节软骨。该研究团队一起发现了一个对关节软骨维持和再生不可或缺的机械敏感的软骨祖细胞群。

据悉，蛋白C受体⁺ (Procr⁺)细胞在多个成体组织中被鉴定为干细胞或祖细胞。然而，机械刺激是否微调它们的激活和分化仍然未知。

附：英文原文

Title: Procr+ chondroprogenitors sense mechanical stimuli to govern articular cartilage maintenance and regeneration

Author: Qiaoling Zhu, Feng Yin, Jiachen Qin, Wanyu Shi, Yaojia Liu, Yuanyuan Zhao, Jianfang Wang, Lei Zhang, Aoyuan Fan, Dandan Cao, Qiqi Peng, Bin Zhou, Lijun Wang, Weiguo Zou, Rui Yue

Issue&Volume: 2025-07-21

Abstract: Protein C receptor+ (Procr+) cells were identified as stem or progenitor cells in multiple adult tissues. However, whether mechanical stimuli fine-tune their activation and differentiation remain unknown. Here, we found rare Procr+ cells in the superficial layer of tibial articular cartilage and meniscus, which keep replenishing chondrocytes in postnatal knee joints. Mechanical stimulation by forced running significantly increased the frequency of Procr+ cells, whereas mechanical unloading by tail suspension showed opposite effects. Osteoarthritis (OA) activated Procr+ cells to repair cartilage erosion, whereas genetic ablation of Procr+ cells accelerated OA progression. Pharmacological or genetic inhibition of the mechanosensor Piezo1 significantly blunted cartilage regeneration by Procr+ cells and exacerbated OA. In contrast, intra-articular administration of a Piezo1 agonist ameliorated OA symptoms. Purified mouse or human Procr+ superficial cells robustly repair articular cartilage after expansion and in vivo transplantation. Together, we discovered a mechanosensitive chondroprogenitor population indispensable for articular cartilage maintenance and regeneration.

DOI: 10.1016/j.cell.2025.06.036

Source: https://www.cell.com/cell/abstract/S0092-8674(25)00738-X