Sumitani Yusuke, Uchibe Kenta, Yoshida Kaya, Weng Yao, Guo Jiajie, Yuan Haoze, Ikegame Mika, Kamioka Hiroshi, Okamura Hirohiko
Department of Orthodontics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.
Department of Oral Morphology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8525, Japan.
Anat Sci Int. 2020 Mar;95(2):202-208. doi: 10.1007/s12565-019-00512-3. Epub 2019 Nov 16.
Retinoic acid (RA), an active metabolite of vitamin A, plays pivotal roles in a wide variety of biological processes, such as body patterning, organ development, and cell differentiation and proliferation. RA signaling is mediated by nuclear retinoic acid receptors, α, β, and γ (RARα, RARβ, and RARγ). RA is a well-known regulator of cartilage and skeleton formation and RARs are also essential for skeletal growth and hypertrophic chondrocyte-specific gene expression. These important roles of RA and RARs in chondrogenesis have been widely investigated using in vivo mouse models. However, few reports are available on the function of each subtype of RARs on in vitro chondrocyte differentiation. Here, we examined the effect of specific agonists of RARs on chondrogenic differentiation of ATDC5 and C3H10T1/2 cells. Subtype-specific RAR agonists as well as RA decreased the expressions of chondrogenic differentiation marker genes and inhibited chondrogenic differentiation, which was accompanied with morphological change to spindle-shaped cells. Among RAR agonists, RARα and RARγ agonists revealed a strong inhibitory effect on chondrogenic differentiation. RARα and RARγ agonists also hampered viability of ATDC5 cells. These observations suggested that RARα and RARγ are dominant receptors of RA signaling that negatively regulate chondrogenic differentiation.
视黄酸（RA）是维生素A的一种活性代谢产物，在多种生物学过程中发挥关键作用，如身体模式形成、器官发育以及细胞分化和增殖。RA信号由核视黄酸受体α、β和γ（RARα、RARβ和RARγ）介导。RA是软骨和骨骼形成的著名调节因子，RARs对骨骼生长和肥大软骨细胞特异性基因表达也至关重要。利用体内小鼠模型已广泛研究了RA和RARs在软骨形成中的这些重要作用。然而，关于RARs各亚型在体外软骨细胞分化中的功能的报道很少。在此，我们研究了RARs特异性激动剂对ATDC5和C3H10T1/2细胞软骨分化的影响。亚型特异性RAR激动剂以及RA降低了软骨分化标记基因的表达并抑制了软骨分化，这伴随着细胞形态变为纺锤形。在RAR激动剂中，RARα和RARγ激动剂对软骨分化显示出强烈的抑制作用。RARα和RARγ激动剂也阻碍了ATDC5细胞的活力。这些观察结果表明，RARα和RARγ是RA信号的主要受体，对软骨分化起负调节作用。
