Increased Sparc release from subchondral osteoblasts promotes articular chondrocyte degeneration under estrogen withdrawal
Increased Sparc release from subchondral osteoblasts promotes articular chondrocyte degeneration under estrogen withdrawal
复制标题
软骨下成骨细胞释放的 Sparc 增加促进雌激素撤退下关节软骨细胞变性
DOI：
10.1016/j.joca.2022.08.020
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发表时间：
2022-12-16
影响因子：
7
通讯作者：
Leng, H.
中科院分区：
文献类型：
--
作者：
Jiang, A.;Xu, P.;Leng, H.
目的：绝经期女性骨关节炎（OA）的发病率明显高于同龄男性。探讨软骨下成骨细胞在雌激素缺乏诱导的OA中的作用，有助于阐明其病理机制，为绝经期OA的诊断和治疗提供新的思路。方法：采用经典的卵巢切除诱导的OA（OVX-OA）大鼠模型，分离原代关节软骨细胞和软骨下成骨细胞，鉴定后在Transwell中共培养。评价软骨细胞合成代谢和分解代谢指标的表达。用液相色谱-质谱联用仪（LC-MS/MS）鉴定成骨细胞条件培养液（CM）中差异表达的蛋白质。用成骨细胞CM处理正常软骨细胞，然后对处理的软骨细胞进行RNA测序。结果：OVX-OA软骨下成骨细胞与软骨细胞共培养后，软骨细胞合成代谢指标的表达显著下调，分解代谢指标的表达显著上调。在正常和OVX成骨细胞培养上清液中鉴定了1，601种蛋白质。蛋白质相互作用网络分析表明，Sparc是其中的一个枢纽蛋白。OVX-OA成骨细胞CM下调软骨细胞AMPK/Foxo 3a信号通路。结论：OVX-OA软骨下成骨细胞分泌的Sparc可下调软骨细胞AMPK/Foxo 3a信号通路，从而促进软骨细胞的退变。(c)2022年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: The incidence of osteoarthritis (OA) in menopausal women is significantly higher than in same-aged men. Investigating the role of subchondral osteoblasts in estrogen deficiency-induced OA may help elucidate the pathological mechanism, providing new insights for the diagnosis and treatment of menopausal OA.Methods: A classical ovariectomy-induced OA (OVX-OA) rat model was utilized to isolate primary articular chondrocytes and subchondral osteoblasts, which were identified and then cocultured in Transwell. The expression of chondrocyte anabolic and catabolic indicators was evaluated. The differ-entially expressed proteins in the conditioned medium (CM) of osteoblasts were identified by Liquid Chromatograph-Mass Spectrometer (LC-MS/MS). Normal chondrocytes were treated with osteoblast CM, and then RNA sequencing was performed on the treated chondrocytes. KEGG was used to identify significant enrichment of signaling pathways, and Simple Western was used to verify the expression of related proteins in the signaling pathways.Results: Coculture of OVX-OA subchondral osteoblasts with chondrocytes significantly downregulated the expression of the anabolic indicators and upregulated the expression of the catabolic indicators in chondrocytes. 1,601 proteins were identified in both normal and OVX osteoblast culture supernatants. Protein-protein interaction network analysis revealed that Sparc was one of the hub proteins. The AMPK/Foxo3a signaling pathway of chondrocytes was downregulated by OVX-OA osteoblasts CM. AICAR, the AMPK agonist, partially reversed the catabolic effect of OVX-OA osteoblasts on chondrocytes.Conclusions: Sparc secreted by OVX-OA subchondral osteoblasts can downregulate the AMPK/Foxo3a signaling pathway of chondrocytes, thereby promoting chondrocyte degeneration.(c) 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.