PMID- 28420144 OWN - NLM STAT- MEDLINE DCOM- 20170629 LR - 20181202 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 4 DP - 2017 Apr 15 TI - Retinoids Regulate Adipogenesis Involving the TGFbeta/SMAD and Wnt/beta-Catenin Pathways in Human Bone Marrow Mesenchymal Stem Cells. LID - 10.3390/ijms18040842 [doi] LID - 842 AB - Retinoids may regulate cell differentiation as ligands of retinoic acid receptors (RARs) and/or retinoid X receptors (RXRs). We showed that RAR agonists promoted adipogenesis by upregulating the expression of CCAAT/enhancer-binding protein beta (C/EBPbeta) in the early stages, but blocked adipogenesis at a later stage in human bone marrow mesenchymal stem cells (hBMSCs). RXR agonists promoted adipogenesis at all time points in hBMSCs. The effect of RAR agonists was mediated mainly by the RARbeta subtype. RAR agonists, in contrast to RXR agonists, significantly promoted the expression of RARbeta. Knockdown of the RARbeta gene via small hairpin RNA (shRNA) attenuated the inhibition of RAR agonists toward adipogenesis. Furthermore, we found that RAR agonists upregulated the transforming growth factor beta (TGFbeta)/SMAD pathway and Wnt/beta-catenin pathway on adipogenesis in hBMSCs, and the stimulating effects were noticeably decreased with the RARbeta gene knockdown. Both RAR agonists and RXR agonists inhibited adipogenesis and blocked the promoter activity of C/EBPbeta and peroxisome proliferator-activated receptor gamma (PPARgamma) in SW872 cell. These results indicated the RAR agonists perform dual roles in adipogenesis in hBMSCs, and the TGFbeta/SMAD pathway and Wnt/beta-catenin pathway may involve the inhibitory effect of RAR agonists. RARbeta is the main receptor subtype mediating the effect. The roles of RXR agonists in adipogenesis exhibited cell type-specific differences, and may be based on the integration of signals from different RXR dimers. FAU - Cao, Jun AU - Cao J AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. Juncao@whu.edu.cn. FAU - Ma, Yuhong AU - Ma Y AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. yuhongma@whu.edu.cn. FAU - Yao, Weiqi AU - Yao W AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. weiqiyao@whu.edu.cn. FAU - Zhang, Xiaoye AU - Zhang X AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. xiaoyezhang@whu.edu.cn. FAU - Wu, Dongcheng AU - Wu D AD - Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China. bcdcwu@hotmail.com. LA - eng PT - Journal Article DEP - 20170415 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (CCAAT-Enhancer-Binding Protein-beta) RN - 0 (PPAR gamma) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Retinoids) RN - 0 (Smad Proteins) RN - 0 (Transforming Growth Factor beta) RN - 0 (retinoic acid receptor beta) SB - IM MH - Adipogenesis/*drug effects/genetics MH - CCAAT-Enhancer-Binding Protein-beta/metabolism MH - Cell Differentiation/drug effects MH - Cell Line MH - Cell Proliferation/drug effects MH - Gene Expression Regulation, Developmental/drug effects MH - Gene Knockdown Techniques MH - Humans MH - Mesenchymal Stem Cells/cytology/*metabolism MH - PPAR gamma/metabolism MH - Receptors, Retinoic Acid/metabolism MH - Retinoid X Receptors/metabolism MH - Retinoids/*pharmacology MH - Smad Proteins/*metabolism MH - Transcriptional Activation/drug effects MH - Transforming Growth Factor beta/*metabolism MH - *Wnt Signaling Pathway PMC - PMC5412426 OTO - NOTNLM OT - TGFbeta/SMAD pathway OT - Wnt/beta-catenin pathway OT - adipogenesis OT - human bone marrow mesenchymal stem cell OT - retinoic acid receptor beta (RARbeta) OT - retinoid COIS- The authors declare no conflict of interest. EDAT- 2017/04/20 06:00 MHDA- 2017/07/01 06:00 PMCR- 2017/04/01 CRDT- 2017/04/20 06:00 PHST- 2017/03/06 00:00 [received] PHST- 2017/03/31 00:00 [revised] PHST- 2017/04/06 00:00 [accepted] PHST- 2017/04/20 06:00 [entrez] PHST- 2017/04/20 06:00 [pubmed] PHST- 2017/07/01 06:00 [medline] PHST- 2017/04/01 00:00 [pmc-release] AID - ijms18040842 [pii] AID - ijms-18-00842 [pii] AID - 10.3390/ijms18040842 [doi] PST - epublish SO - Int J Mol Sci. 2017 Apr 15;18(4):842. doi: 10.3390/ijms18040842.