Faculty of Medicine and Health, Leeds Institute of Rheumatoid and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
School of Mechanical Engineering, Institute of Medical and Biological Engineering, University of Leeds, Leeds, UK.
J Cell Mol Med. 2021 Jan;25(1):259-271. doi: 10.1111/jcmm.15993. Epub 2020 Dec 11.
A large proportion of ankle osteoarthritis (OA) has an early onset and is post-traumatic. Surgical interventions have low patient satisfaction and relatively poor clinical outcome, whereas joint-preserving treatments, which rely on endogenous multipotential stromal cells (MSCs), result in suboptimal repair. This study investigates MSC presence and potency in OA-affected talocrural osteochondral tissue. Bone volume fraction (BV/TV) changes for the loading region trabecular volume and subchondral bone plate (SBP) thickness in OA compared with healthy tissue were investigated using microcomputed tomography. CD271-positive MSC topography was related to bone and cartilage damage in OA tissue, and in vitro MSC potency was compared with control healthy iliac crest (IC) MSCs. A 1.3- to 2.5-fold SBP thickening was found in both OA talus and tibia, whereas BV/TV changes were depth-dependent. MSCs were abundant in OA talus and tibia, with similar colony characteristics. Tibial and talar MSCs were tripotential, but talar MSCs had 10-fold lower adipogenesis and twofold higher chondrogenesis than IC MSCs (P = .01 for both). Cartilage damage in both OA tibia and talus correlated with SBP thickening and CD271+ MSCs was 1.4- to twofold more concentrated near the SBP. This work shows multipotential MSCs are present in OA talocrural subchondral bone, with their topography suggesting ongoing involvement in SBP thickening. Potentially, biomechanical stimulation could augment the chondrogenic differentiation of MSCs for joint-preserving treatments.
大量踝关节骨关节炎（OA）发病早且为创伤后性。手术干预的患者满意度低，临床效果相对较差，而依赖内源性多能基质细胞（MSCs）的关节保留治疗则导致修复效果不佳。本研究调查了 OA 影响的距下关节骨软骨组织中 MSC 的存在和效力。通过微计算机断层扫描，研究了 OA 与健康组织相比，负重区小梁体积和软骨下骨板（SBP）厚度的骨体积分数（BV/TV）变化。CD271 阳性 MSC 分布与 OA 组织中的骨和软骨损伤有关，并比较了体外 MSC 效力与对照健康髂嵴（IC）MSCs。OA 距骨和胫骨的 SBP 均增厚了 1.3 到 2.5 倍，而 BV/TV 变化则与深度有关。OA 距骨和胫骨中有丰富的 MSC，其集落特征相似。胫骨和距骨 MSC 具有三向分化潜能，但距骨 MSC 的成脂能力比 IC MSC 低 10 倍，软骨形成能力高 2 倍（均 P =.01）。OA 胫骨和距骨的软骨损伤与 SBP 增厚相关，CD271+MSC 靠近 SBP 的浓度增加了 1.4 到 2 倍。这项工作表明，多能 MSC 存在于 OA 距下关节软骨下骨中，其分布提示其持续参与 SBP 增厚。潜在地，生物力学刺激可以增强 MSC 的软骨分化，用于关节保留治疗。
