Saneshige S, Mano H, Tezuka K, Kakudo S, Mori Y, Honda Y, Itabashi A, Yamada T, Miyata K, Hakeda Y
Fourth Department of Internal Medicine, Saitama Medical School, Japan.
Biochem J. 1995 Aug 1;309 ( Pt 3)(Pt 3):721-4. doi: 10.1042/bj3090721.
Vitamin A metabolites such as all-trans-retinoic acid (all-trans-RA) affect several steps of metabolic processes in vertebrates. In the last few years, several studies have shown the effect of RA on bone formation and metabolism. However, mechanisms of its action still remain unclear, especially with respect to the regulation of bone cells. Therefore, this study was carried out to clarify how RA regulates the activity of osteoclasts. Using a pit assay involving unfractionated bone cells, including osteoclasts obtained from rabbits, we found that RA stimulated an increase in the bone-resorbing activity in a dose- and time-dependent manner. Furthermore, this effect occurred more rapidly than that of treatments with 1 alpha,25-dihydroxyvitamin D3. However, this effect of RA may be partly related to cross-talk between osteoclasts and other types of cells. Therefore we studied the effect of RA on isolated osteoclasts. We found that all-trans-RA regulates the gene expression of cathepsin K/OC-2, a dominant cysteine proteinase, at the transcriptional level in mature osteoclasts isolated from rabbits. Moreover, retinoic acid-receptor alpha mRNA and retinoid X-receptor beta mRNA were expressed in these mature osteoclasts. Our results indicate that osteoclasts are target cells for RA and that RA might regulate a part of bone formation and metabolism through osteoclasts.
维生素A代谢产物如全反式维甲酸（all-trans-RA）会影响脊椎动物代谢过程的多个步骤。在过去几年中，多项研究显示了维甲酸对骨形成和代谢的影响。然而，其作用机制仍不清楚，特别是在骨细胞的调控方面。因此，开展本研究以阐明维甲酸如何调节破骨细胞的活性。通过使用涉及未分离骨细胞（包括从兔子获得的破骨细胞）的骨吸收陷窝分析，我们发现维甲酸以剂量和时间依赖性方式刺激骨吸收活性增加。此外，这种作用比用1α,25-二羟基维生素D3处理出现得更快。然而，维甲酸的这种作用可能部分与破骨细胞和其他类型细胞之间的相互作用有关。因此我们研究了维甲酸对分离的破骨细胞的作用。我们发现全反式维甲酸在转录水平上调节从兔子分离的成熟破骨细胞中组织蛋白酶K/OC-2（一种主要的半胱氨酸蛋白酶）的基因表达。此外，维甲酸受体α mRNA和视黄酸X受体β mRNA在这些成熟破骨细胞中表达。我们的结果表明破骨细胞是维甲酸的靶细胞，并且维甲酸可能通过破骨细胞调节部分骨形成和代谢。
