title: The role of retinoic acid receptor inhibitor LE135 on the osteochondral differentiation of human bone marrow mesenchymal stem cells.
abstract: The present study aimed to investigate the role of a retinoic acid receptor-β (RARβ) inhibitor LE135 on TGF-β induced chondrogenesis of human bone marrow mesenchymal stem cells (hMSCs). Pellet culture with exogenous transforming growth factor-β (TGF-β), and a mechanically loaded scaffold system were used to provide two culture models. All samples were cultured for 8 days and changes in early gene expression were determined. Glycosaminoglycan and mRNA expression data showed that LE135 itself did not induce any chondrogenic response in either pellet culture or scaffold culture of hMSCs. LE135 actually inhibited the chondrogenic response caused by exogenous TGF-β, or endogenous TGF-β induced by mechanical load, while the expression of genes normally associated with osteogenesis was not affected. This suggests that the inhibitor LE135 affects the osteochondral differentiation pathway at a different stage, inhibiting chondrogenic gene expression while having no effect on genes normally associated with the osteogenic phenotype. Alternatively, it might be that different cells were proceeding down different lineages. Some cells were undergoing chondrogenesis and this was affected by LE135, while other cells underwent osteogenic differentiation and were not affected by LE135.
authors.affiliation: AO Research Institute, AO Foundation, Davos Platz 7270, Switzerland.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Shan-Jing
authors.initials: SJ
authors.lastname: Yao
authors.forename: Mauro
authors.initials: M
authors.lastname: Alini
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stoddart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D003984:Dibenzazepines / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology / Q000187:drug effects; D049230:Retinoid X Receptor beta / Q000037:antagonists & inhibitors* / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D003984:Dibenzazepines; C104182:LE 135; D049230:Retinoid X Receptor beta; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D016212:Transforming Growth Factor beta; D004247:DNA