Identification of human temporomandibular joint fibrocartilage stem cells with distinct chondrogenic capacity

Identification of human temporomandibular joint fibrocartilage stem cells with distinct chondrogenic capacity
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具有独特成软骨能力的人颞下颌关节纤维软骨干细胞的鉴定

DOI:
10.1016/j.joca.2020.02.835
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发表时间:
2020-06-01
影响因子:
7
通讯作者:
Zhu, S.
Zhu, S.
中科院分区:
医学2区
文献类型:
--
作者:
Bi, R.;Yin, Q.;Zhu, S.

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目的:本研究旨在鉴定人纤维软骨干细胞(hFCSCs)在软骨内环境稳定和修复过程中的细胞定位、干细胞特性,并探讨其向软骨分化的调控机制。比较hFCSCs与hOFMSCs在体外和体内的成软骨潜能。通过体外shRNA干扰和GFP(+)FCSCs处理大鼠髁突软骨缺损模型,研究SOX 9在FCSCs成软骨过程中的调控作用。结果:hFCSCs具有典型的间充质干细胞特征,与hOFMSCs相比,具有更强的软骨形成能力。此外,hFCSC显示显著增加的SOX 9表达。在软骨颗粒培养过程中,hFCSCs中SOX 9的表达强于hOFMSCs。SOX9 shRNA干扰下调hFCSCs体外成软骨能力,以及破坏GFP thorn FCSCs向大鼠髁突软骨缺损中成熟软骨细胞的迁移和成软骨分化。值得注意的是,SOX 9的表达也被发现抑制在髁突浅区TMJOA patients.Conclusion:我们发现在人TMJ软骨中存在FCSCs,并表征其独特的干细胞特征。SOX9是hFCSCs向软骨细胞分化的关键因子,全面了解SOX9在hFCSCs中的调控作用对探索TMJ紊乱时髁突软骨降解的干预策略具有重要意义。(C)2020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: This study was aimed to identify the residence of human fibrocartilage stem cells (hFCSCs), characterize their stem cell properties and investigate the functional mechanisms which regulate fibrocartilage stem cells (FCSCs) toward chondrogenic differentiation during cartilage homeostasis and repairing.Methods: Cytological characteristics of hFCSCs and human orofacial mesenchymal stem cells (hOFMSCs) were analyzed. Chondrogenic potential of hFCSCs was compared with hOFMSCs both in vitro and in vivo. Regulatory role of SOX9 during FCSCs chondrogenesis was studied by shRNA interference in vitro, and by GFP(+) FCSCs treatment in rat condylar cartilage defect model. SOX9 expression was also examined in temporomandibular joint osteoarthritis (TMJOA) patients' cartilage surface.Results: hFCSCs exhibited typical mesenchymal stem cell characteristics, with significantly stronger chondrogenic capability compared to hOFMSCs. Moreover, hFCSCs showed remarkably increased expression of SOX9. During cartilage pellet culture, there was stronger SOX9 expression in hFCSCs than hOFMSCs. SOX9 shRNA interference downregulated chondrogenic capability of hFCSCs in vitro, as well as disrupting migration and chondrogenic differentiation of GFPthorn FCSCs toward mature chondrocytes in rat condylar cartilage defect. Of note, SOX9 expression was also found suppressed in the condylar superficial zone of TMJOA patients.Conclusion: We found the existence of FCSCs in human TMJ cartilage, and characterized their distinct stem cell features. SOX9 is essential for hFCSCs chondrogenic differentiation, and a comprehensive understanding of the regulatory role of SOX9 in hFCSCs would be important for exploring potential intervention strategy of condylar cartilage degradation during TMJ disorders. (C) 2020 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.