Nuka S, Sawada N, Iba K, Chiba H, Ishii S, Mori M
Department of Pathology, Sapporo Medical University School of Medicine, Japan.
Cell Struct Funct. 1997 Feb;22(1):27-32. doi: 10.1247/csf.22.27.
We have recently established a human osteoblastic cell line (SV-HFO) in a culture system, in which the cells are mineralized by treatment with dexamethasone (Dex). Using this system, we examined the effects of all trans-retinoic acid (RA) on the mineralization of the cells. RA inhibited the mineralization, coincident with the inhibition of alkaline phosphatase (ALP). On the other hand, RA induced osteocalcin secretion and had no effect on the expression of the other osteoblastic markers such as type I collagen and osteonectin. To further clarify the mechanism of inhibition of mineralization by RA, we used the retinoic acid receptor (RAR) alpha-selective (Am80), beta-selective (CD2019) and gamma-selective (CD437) agonists instead of RA. RAR alpha- and RAR beta-selective agonists inhibited the mineralization and ALP activity of the cells, while the RAR gamma-selective agonist had no such effects. On the other hand, the RAR gamma-selective agonist induced osteocalcin secretion, but RAR alpha- and RAR beta-selective agonists had no effect on osteocalcin secretion. These results suggested that the inhibitory effect of RA on the mineralization of human osteoblasts is mediated by the activation of RAR alpha and/or RAR beta and that RAR gamma preferentially regulates the expression of osteocalcin without influence on mineralization.
我们最近在一种培养系统中建立了一种人成骨细胞系（SV-HFO），在该系统中，细胞经地塞米松（Dex）处理后会发生矿化。利用这个系统，我们研究了全反式维甲酸（RA）对细胞矿化的影响。RA抑制了矿化，同时也抑制了碱性磷酸酶（ALP）。另一方面，RA诱导了骨钙素的分泌，并且对其他成骨细胞标志物如I型胶原蛋白和骨连接蛋白的表达没有影响。为了进一步阐明RA抑制矿化的机制，我们使用了维甲酸受体（RAR）α选择性激动剂（Am80）、β选择性激动剂（CD2019）和γ选择性激动剂（CD437）来替代RA。RARα和RARβ选择性激动剂抑制了细胞的矿化和ALP活性，而RARγ选择性激动剂没有这种作用。另一方面，RARγ选择性激动剂诱导了骨钙素的分泌，但RARα和RARβ选择性激动剂对骨钙素的分泌没有影响。这些结果表明，RA对人成骨细胞矿化的抑制作用是由RARα和/或RARβ的激活介导的，并且RARγ优先调节骨钙素的表达而不影响矿化。
