Mesenchymal stem/ stromal cell (MSC) exhaustion has been suggested to be a hallmark of aging. Osteoarthritis has a complex etiology that comprises several factors. Dysplasia has been shown to be an individual risk factor for osteoarthritis. Subchondral bone changes are often the first detectable alterations in osteoarthritis. In this study, we aimed to determine whether skeletal MSCs are differentially affected in patients with primary versus dysplastic osteoarthritis. Patients undergoing hip arthroplasty due to primary osteoarthritis (n = 11) and osteoarthritis with hip dysplasia (n = 10) were included in the study. Femoral head subchondral bone was used for isolation of MSCs. The cells were compared using detailed ex-vivo and in-vitro analyses, which included immunophenotyping, colony-forming-unit fibroblast assay, growth kinetics, senescence, multilineage potential, immunophenotyping, and MSC marker-gene expression profiling. Isolated cells from primary osteoarthritis patients showed decreased viability in comparison with those from dysplasia patients, with similar mesenchymal fractions (i.e., CD45/ CD19/ CD14/ CD34-negative cells). In-vitro expanded MSCs from primary osteoarthritis patients showed reduced osteogenic and chondrogenic potential in comparison with dysplasia patients. There were no differences in clonogenicity, growth kinetics, senescence, adipogenic potential, and immunophenotype between these groups. Gene expression profiling showed well-known marker of bone marrow MSCs, the leptin receptor, to be significantly lower for primary osteoarthritis patients. Our study shows that the pathology of primary osteoarthritis is accompanied by bone MSC exhaustion, while biomechanical dysfunction associated with hip dysplasia can induce secondary osteoarthritis without this MSC impairment. Our study suggests that subchondral bone MSC exhaustion is implicated in the pathology of primary osteoarthritis.

中文翻译：

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原发性增生性骨关节炎与软骨下骨源间充质干细胞/基质细胞的疲惫增加。

间充质干/基质细胞（MSC）衰竭被认为是衰老的标志。骨关节炎的病因复杂，包括几个因素。发育不良已被证明是骨关节炎的个体危险因素。软骨下骨改变通常是骨关节炎中最先被发现的改变。在这项研究中，我们旨在确定原发性与增生性骨关节炎患者中骨骼肌MSC是否受到差异影响。因原发性骨关节炎（n  = 11）和伴有髋关节发育不良的骨关节炎（n = 10）被纳入研究。股骨头软骨下骨用于分离MSC。使用详细的离体和体外分析比较细胞，包括免疫表型分析，集落形成单位成纤维细胞分析，生长动力学，衰老，多谱系潜能，免疫表型分析和MSC标记基因表达谱分析。与不典型增生患者分离的细胞相比，原发性骨关节炎患者分离的细胞显示出降低的活力，具有相似的间充质成分（即CD45 / CD19 / CD14 / CD34阴性细胞）。与非典型增生患者相比，原发性骨关节炎患者的体外扩增的MSC显示出降低的成骨和软骨形成潜能。这些组之间的克隆形成性，生长动力学，衰老，成脂潜能和免疫表型没有差异。基因表达谱显示，骨髓MSCs的瘦素受体众所周知的标志物，对于原发性骨关节炎患者而言明显更低。我们的研究表明，原发性骨关节炎的病理学表现为骨骼MSC衰竭，而与髋关节发育不良相关的生物力学功能障碍可诱发继发性骨关节炎，而无MSC损伤。我们的研究表明，软骨下骨MSC衰竭与原发性骨关节炎的病理学有关。而与髋关节发育不良相关的生物力学功能障碍可诱发继发性骨关节炎，而无此MSC损伤。我们的研究表明，软骨下骨MSC衰竭与原发性骨关节炎的病理学有关。而与髋关节发育不良相关的生物力学功能障碍可诱发继发性骨关节炎，而无此MSC损伤。我们的研究表明，软骨下骨MSC衰竭与原发性骨关节炎的病理学有关。