Cartilage loss leads to osteoarthritis, the most common cause of disability for which there is no cure. Cartilage regeneration, therefore, is a priority in medicine. We report that agrin is a potent chondrogenic factor and that a single intraarticular administration of agrin induced long-lasting regeneration of critical-size osteochondral defects in mice, with restoration of tissue architecture and bone-cartilage interface. Agrin attracted joint resident progenitor cells to the site of injury and, through simultaneous activation of CREB and suppression of canonical WNT signaling downstream of β-catenin, induced expression of the chondrogenic stem cell marker GDF5 and differentiation into stable articular chondrocytes, forming stable articular cartilage. In sheep, an agrin-containing collagen gel resulted in long-lasting regeneration of bone and cartilage, which promoted increased ambulatory activity. Our findings support the therapeutic use of agrin for joint surface regeneration.

软骨损失导致骨关节炎，这是导致残疾的最常见原因，目前尚无治愈方法。因此，软骨再生是医学上的优先事项。我们报告说，集聚蛋白是一种有效的软骨形成因子，单次关节内给药集聚蛋白可诱导小鼠临界尺寸骨软骨缺损的持久再生，并恢复组织结构和骨-软骨界面。Agrin 将关节驻留祖细胞吸引到损伤部位，并通过同时激活 CREB ​​和抑制 β-catenin 下游的经典 WNT 信号，诱导软骨形成干细胞标志物 GDF5 的表达并分化为稳定的关节软骨细胞，形成稳定的关节软骨. 在绵羊中，含有集聚蛋白的胶原蛋白凝胶导致骨骼和软骨的长期再生，从而促进了门诊活动的增加。我们的研究结果支持集聚蛋白在关节表面再生中的治疗用途。