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人脂肪间充质干细胞对炎症应激诱导的骨关节炎软骨细胞衰老特征的旁分泌作用

Paracrine effects of human adipose-derived mesenchymal stem cells in inflammatory stress-induced senescence features of osteoarthritic chondrocytes.

作者信息

Platas Julia, Guillén Maria Isabel, Pérez Del Caz Maria Dolores, Gomar Francisco, Castejón Miguel Angel, Mirabet Vicente, Alcaraz Maria José

机构信息

Department of Pharmacology and IDM, University of Valencia, Burjasot, 46100 Valencia, Spain.

Department of Pharmacy, Cardenal Herrera-CEU University, Moncada, 46113 Valencia, Spain.

出版信息

Aging (Albany NY). 2016 Aug;8(8):1703-17. doi: 10.18632/aging.101007.

DOI:10.18632/aging.101007
PMID:27490266
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5032691/
Abstract

Aging and exposure to stress would determine the chondrocyte phenotype in osteoarthritis (OA). In particular, chronic inflammation may contribute to stress-induced senescence of chondrocytes and cartilage degeneration during OA progression. Recent studies have shown that adipose-derived mesenchymal stem cells exert paracrine effects protecting against degenerative changes in chondrocytes. We have investigated whether the conditioned medium (CM) from adipose-derived mesenchymal stem cells may regulate senescence features induced by inflammatory stress in OA chondrocytes. Our results indicate that CM down-regulated senescence markers induced by interleukin-1β including senescence-associated β-galactosidase activity, accumulation of γH2AX foci and morphological changes with enhanced formation of actin stress fibers. Treatment of chondrocytes with CM also decreased the production of oxidative stress, the activation of mitogen-activated protein kinases, and the expression of caveolin-1 and p21. The effects of CM were related to the reduction in p53 acetylation which would be dependent on the enhancement of Sirtuin 1 expression. Therefore, CM may exert protective effects in degenerative joint conditions by countering the premature senescence of OA chondrocytes induced by inflammatory stress.

摘要

衰老和应激暴露会决定骨关节炎（OA）中的软骨细胞表型。特别是，慢性炎症可能在OA进展过程中促成应激诱导的软骨细胞衰老和软骨退变。最近的研究表明，脂肪来源的间充质干细胞发挥旁分泌作用，保护软骨细胞免受退行性变化影响。我们研究了来自脂肪来源间充质干细胞的条件培养基（CM）是否可调节OA软骨细胞中炎症应激诱导的衰老特征。我们的结果表明，CM下调了白细胞介素-1β诱导的衰老标志物，包括衰老相关β-半乳糖苷酶活性、γH2AX焦点的积累以及肌动蛋白应激纤维形成增强的形态学变化。用CM处理软骨细胞还降低了氧化应激的产生、丝裂原活化蛋白激酶的激活以及小窝蛋白-1和p21的表达。CM的作用与p53乙酰化的减少有关，这将依赖于沉默调节蛋白1表达的增强。因此，CM可能通过对抗炎症应激诱导的OA软骨细胞过早衰老，在退行性关节疾病中发挥保护作用。

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