Intraarticular senescent chondrocytes impair the cartilage regeneration capacity of mesenchymal stem cells

Intraarticular senescent chondrocytes impair the cartilage regeneration capacity of mesenchymal stem cells
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关节内衰老软骨细胞损害间充质干细胞的软骨再生能力

DOI:
10.1186/s13287-019-1193-1
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发表时间:
2019-03-12
影响因子:
7.5
通讯作者:
Wu, Song
Wu, Song
中科院分区:
医学2区
文献类型:
--
作者:
Cao, Xu;Luo, Pan;Wu, Song

文献摘要

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背景色细胞对周围细胞环境产生了重大影响。发现衰老的软骨细胞(Snchos)在受骨关节炎影响的关节中存在于软骨中积累。尚未报道Snchos对外源移植的干细胞的影响。这项研究方法,我们评估了SNCHOS与骨髓间充质干细胞(BMSC)之间的相互作用(BMSC)以及在关节内渗透性微环境(IASM)时(IASM)(IASM)(IASM) )。还评估了IASM对软骨再生的影响。结果发现,SNCHOS诱导的BMSC细胞衰老和凋亡的一小部分。 SNCHOS还抑制了BMSC的增殖,促进的茎和抑制软骨分化。 BMSC诱导了Snchos的凋亡,减少了Snchos的比例,刺激了Snchos增殖,并揭示了对Snchos炎症的双向作用。 IASM显着抑制了体内移植BMSC的存活,增殖和适当的分化,所有这些BMSC都损害了软骨再生。抗染色剂ABT-263能够从SNCHOS的负面影响中部分挽救细胞。Conconconconconconconconconconconconconconconconthossnchos和bmscs在细胞衰老,凋亡,增殖,分化和细胞功能时相互相互作用。这种相互作用损害了MSC的软骨修复。抗染色剂为这种损害提供了可能的解决方案。
BackgroundSenescent cells exert a significant influence over their surrounding cellular environment. Senescent chondrocytes (SnChos) were found to be accumulated in degenerated cartilage present in joints affected by osteoarthritis. The influence of SnChos on exogenously transplanted stem cells has yet to be reported.MethodsIn this study, we evaluated the interactions between SnChos and bone marrow mesenchymal stem cells (BMSCs) when co-cultured as well as in the intra-articular senescent microenvironment (IASM). The effect of IASM on cartilage regeneration was also assessed.ResultsIt was found that a small fraction of SnChos induced BMSC cellular senescence and apoptosis. SnChos also inhibited proliferation, facilitated stemness, and suppressed chondrogenic differentiation of BMSCs. BMSCs induced the apoptosis of SnChos, reduced the proportion of SnChos, stimulated SnChos proliferation, and revealed a bidirectional effect on SnChos inflammaging. IASM significantly suppressed the survival, proliferation, and appropriate differentiation of grafted BMSCs in vivo, all of which impaired cartilage regeneration. Anti-senescence agent ABT-263 was able to partly rescue the cells from the negative effects of SnChos.ConclusionsThe SnChos and BMSCs interacted with each other at cellular senescence, apoptosis, proliferation, differentiation, and cell functions. This interaction impaired the cartilage repair of MSCs. Anti-senescence agent provided a possible solution for this impairment.