早发性骨关节炎起源于髋关节发育不良的软骨细胞水平。,Scientific Reports

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早发性骨关节炎起源于髋关节发育不良的软骨细胞水平。
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-17 , DOI: 10.1038/s41598-020-57431-x
Paula A Hernandez ₁ , Joel Wells ₁ , Emiliya Usheva ₁ , Paul A Nakonezny ₂ , Zahra Barati ₁ , Roberto Gonzalez ₁ , Layla Kassem ₁ , Frances M D Henson ₃

Affiliation

髋关节发育不良（DDH）的受试者常表现为早发性骨关节炎（OA）；但是，尚不清楚这种病理学的分子机制。我们调查了在变性的组织学表现之前，是否可以在来自DDH软骨的软骨细胞中检测到来自OA软骨的软骨细胞的细胞变化。我们对22例接受和不接受DDH（9 DDH-OA，仅12 OA，1个股骨骨折）的髋关节置换手术的参与者进行了未受损和受损关节软骨的研究。组织免疫染色显示受损的仅OA软骨发生了变化，这种变化也在未受损的DDH-OA软骨中发现。两组的原位软骨细胞均显示：（i）波形蛋白中间丝的较粗纤维，（ii）整联蛋白α5β1簇，（iii）MMP13染色阳性，以及（iv）表达丝氨酸蛋白酶HtrA1的细胞比例更高。细胞外基质的进一步表征显示在未损伤的DDH软骨中有强聚集蛋白聚糖和II型胶原蛋白的免疫染色，没有证据表明caspase 3活化会增加细胞死亡。这些发现表明DDH软骨的早期事件起源于软骨细胞水平，并且DDH软骨可能为研究这些早期变化为OA治疗靶标的开发提供了新的机会。

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Early-Onset Osteoarthritis originates at the chondrocyte level in Hip Dysplasia.

Subjects with developmental dysplasia of the hip (DDH) often show early-onset osteoarthritis (OA); however, the molecular mechanisms underlying this pathology are not known. We investigated whether cellular changes in chondrocytes from OA cartilage can be detected in chondrocytes from DDH cartilage before histological manifestations of degeneration. We characterized undamaged and damaged articular cartilage from 22 participants having hip replacement surgery with and without DDH (9 DDH-OA, 12 OA-only, one femoral fracture). Tissue immunostaining revealed changes in damaged OA-only cartilage that was also found in undamaged DDH-OA cartilage. Chondrocytes in situ from both groups show: (i) thicker fibers of vimentin intermediate filaments, (ii) clusters of integrin α5β1, (iii) positive MMP13 staining and (iv) a higher percentage of cells expressing the serine protease HtrA1. Further characterization of the extracellular matrix showed strong aggrecan and collagen II immunostaining in undamaged DDH cartilage, with no evidence of augmented cell death by activation of caspase 3. These findings suggest that early events in DDH cartilage originate at the chondrocyte level and that DDH cartilage may provide a novel opportunity to study these early changes for the development of therapeutic targets for OA.

更新日期：2020-01-17

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