The role of native (not culture-expanded) joint-resident mesenchymal stem cells (MSCs) in the repair of joint damage in osteoarthritis (OA) is poorly understood. MSCs differ from bone marrow-residing haematopoietic stem cells in that they are present in multiple niches in the joint, including subchondral bone, cartilage, synovial fluid, synovium and adipose tissue. Research in experimental models suggests that the migration of MSCs adjacent to the joint cavity is crucial for chonodrogenesis during embryogenesis, and also shows that synovium-derived MSCs might be the primary drivers of cartilage repair in adulthood. In this Review, the available data is synthesized to produce a proposed model in which joint-resident MSCs with access to superficial cartilage are key cells in adult cartilage repair and represent important targets for manipulation in 'chondrogenic' OA, especially in the context of biomechanical correction of joints in early disease. Growing evidence links the expression of CD271, a nerve growth factor (NGF) receptor by native bone marrow-resident MSCs to a wider role for neurotrophins in OA pathobiology, the implications of which require exploration since anti-NGF therapy might worsen OA. Recognizing that joint-resident MSCs are comparatively abundant in vivo and occupy multiple niches will enable the optimization of single-stage therapeutic interventions for OA.

天然（非培养扩展）的关节驻留间充质干细胞（MSC）在骨关节炎（OA）关节损伤修复中的作用了解得很少。MSC与驻留骨髓的造血干细胞不同，它们存在于关节的多个壁ni中，包括软骨下骨，软骨，滑液，滑膜和脂肪组织。实验模型的研究表明，邻近关节腔的MSC的迁移对于胚胎发生过程中的软骨形成至关重要，并且还表明滑膜衍生的MSC可能是成年软骨修复的主要驱动力。在这篇评论中，合成现有数据以产生一个提出的模型，其中可接触浅表软骨的关节居间MSC是成年软骨修复的关键细胞，并代表“软骨生成” OA操作的重要目标，尤其是在对关节进行生物力学校正的情况下早期疾病。越来越多的证据将天然骨髓驻留MSC的神经生长因子（NGF）受体CD271的表达与OA病理学中神经营养蛋白的更广泛作用联系起来，由于抗NGF疗法可能使OA恶化，因此需要进一步探讨其含义。认识到共同居住的MSC相对丰富 天然骨髓驻留MSCs产生的神经生长因子（NGF）受体在OA病理生物学中对神经营养蛋白具有更广泛的作用，由于抗NGF疗法可能使OA恶化，因此需要进一步探讨其含义。认识到共同居住的MSC相对丰富 天然骨髓驻留MSCs产生的神经生长因子（NGF）受体在OA病理生物学中对神经营养蛋白具有更广泛的作用，由于抗NGF疗法可能使OA恶化，因此需要进一步探讨其含义。认识到共同居住的MSC相对丰富在体内并占据多个位置将使OA的单阶段治疗干预措施最优化。