Abstract
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.
Highlights
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan composed of repeating disaccharides of glucuronic acid and N-acetylglucosamine [1, 2]
GSK facilitated the expression of chondrogenic markers, as measured by the mRNA levels of SOX9 and Aggrecan, in ATDC5 cells by transient receptor potential vanilloid 4 (TRPV4) activation in a dose- and a time-dependent manner (Fig 1A and 1B)
Pericellular HA was reported to be involved in TRPV4-induced chondrogenesis via association with both Intracellular adhesion molecule-1 (ICAM-1) and CD44
Summary
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan composed of repeating disaccharides of glucuronic acid and N-acetylglucosamine [1, 2]. HA plays an essential role in the homeostasis of cartilage-related tissues [3,4,5], suggesting that it is required for chondrogenesis. It protects human osteoarthritic chondrocytes by reducing oxidative stress, apoptosis, and mediators of inflammation and catabolism in those tissues [6]. Intracellular adhesion molecule-1 (ICAM-1) and CD44 have been identified as the major receptors for HA [8,9,10].
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