Hyaluronan promotes TRPV4-induced chondrogenesis in ATDC5 cells
Hyaluronan promotes TRPV4-induced chondrogenesis in ATDC5 cells
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DOI：
10.1371/journal.pone.0219492
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发表时间：
2019-08-08
期刊：
影响因子：
3.7
通讯作者：
Kojima, Toshihisa
中科院分区：
文献类型：
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作者：
Ogawa, Yoshikazu;Takahashi, Nobunori;Kojima, Toshihisa
透明质酸(HA)是一种细胞外基质糖胺聚糖，对软骨相关组织的动态平衡是必不可少的。细胞内黏附分子-1(ICAM-1)和CD44是透明质酸的受体。近年来，瞬时受体电位香草素4(TRPV4)已成为多个生理学领域的潜在研究靶点。TRPV4是一种钙离子渗透性的非选择性阳离子通道，在几种肌肉骨骼组织中似乎具有机械感觉或渗透感觉作用。HA和TRPV4在软骨形成中起关键作用；然而，目前还不清楚它们是否对软骨形成有交互作用，如果是，它们是如何相互作用的？本研究利用ATDC5细胞系研究了HA及其受体ICAM-1、CD44和TRPV4在软骨形成过程中的相互关系。研究发现，在TRPV4诱导的软骨形成中，HA的存在是必需的。HA的缺失抑制了TRPV4诱导的软骨标志物SOX9和Aggrecan的表达。此外，HA部分通过ICAM-1和CD44影响TRPV4诱导的软骨形成。综上所述，首次报道了在ATDC5细胞系中存在HA、其受体ICAM-1和CD44之间的相互作用以及TRPV4-活性在软骨形成中的作用。已知TRPV4在多种肌肉骨骼组织中起机械感觉通道的作用。因此，这项研究的结果可能表明存在一种分子机制，该机制是HA和机械载荷在关节软骨形成中相互作用的基础。
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan essential for the homeostasis of cartilage-related tissues. Intracellular adhesion molecule-1 (ICAM-1) and CD44 have been identified as receptors for HA. Recently, transient receptor potential vanilloid 4 (TRPV4) has emerged as a potential research target in several areas of physiology. TRPV4 is a Ca2+-permeable, non-selective cation channel that appears to have mechanosensory or osmosensory roles in several musculoskeletal tissues. HA and TRPV4 play key roles in chondrogenesis; however, it has remained unclear whether they have interactive effects on chondrogenesis and, if so, how do they interact with each other? This study investigated the relationship between HA, its receptors ICAM-1 and CD44, and TRPV4 in the chondrogenic pathway using the ATDC5 cell line. It was found that the presence of HA is required for TRPV4-induced chondrogenesis. Loss of HA suppressed TRPV4-induced expression of the chondrogenic markers, SOX9 and Aggrecan. Moreover, HA affects TRPV4-induced chondrogenic development via each of ICAM-1 and CD44 partially. In conclusion, for the first time, the existence of an interaction between HA, its receptor ICAM-1 and CD44, and TRPV4-activity in chondrogenesis in the ATDC5 cell line was reported. TRPV4 is known to function as a mechanosensory channel in several musculoskeletal tissues. Therefore, findings of this study may suggest the existence of a molecular mechanism that underlies the interactive effects of HA and mechanical loading on joint chondrogenesis.