Retinoic acid inhibits osteogenic differentiation of rat bone marrow stromal cells.
It has been well established that all-trans-retinoic acid (ATRA) influences bone metabolism when given in the treatment or prevention of cancer. However, the molecular mechanisms underlying this are unknown. In the present study, we investigated the effect of ATRA on differentiation of rat bone marrow stromal cells (BMSCs). BMSCs were harvested from rats and induced to differentiate in the presence or absence of ATRA in either osteogenic (OM) or control medium (CM). BMSCs underwent osteogenic differentiation, showed alkaline phosphatase (ALP) activity, a high level of matrix mineralization, and expressed osteonectin when cultured in OM. Although ATRA induced ALP activity, it failed to induce matrix mineralization and osteonectin, decrease mineralization in OM, and induce lipid accumulation in BMSCs. Moreover, while ATRA induced the expression of BMP-RIA, both BMP-RII and Smad5 mRNA were induced by OM and ATRA. Thus, ATRA inhibited osteogenesis and promoted adipogenesis of BMSCs. BMP signaling cooperated with ATRA in the differentiation of BMSCs.
Wang
Anxun
A
Department of Oral and Maxillofacial surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 zhongshan Road II, Guangzhou, Guangdong 510080, PR China.
Ding
Xueqiang
X
Sheng
Shihu
S
Yao
Zhaoyou
Z
D050156:Adipogenesis / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000096:biosynthesis; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051902:Smad5 Protein / Q000096:biosynthesis; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
D012333:RNA, Messenger; D051902:Smad5 Protein; C497799:Smad5 protein, rat; D014212:Tretinoin; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D000469:Alkaline Phosphatase