Role of retinoic acid-related orphan receptor-α in differentiation of human mesenchymal stem cells along with osteoblastic lineage

Objective: In a human mesenchymal stem cell (hMSC) model of osteoblast differentiation, we identified expression of the retinoic acid-related orphan receptor-α (RORα) gene as a candidate osteogenesis-related gene using gene expression profiling. RORα is a member of the nuclear receptor family of intracellular transcription factors and plays multifunctional roles in tissue development and differentiation, inflammation metabolism and circadian rhythms. However, the important role of RORα in the differentiation of hMSC along the osteoblastic lineage is not yet fully understood. Methods: To investigate the role of RORα during osteoblast differentiation, we eliminated RORα from hMSCs with a small interfering RNA molecule (siRNA), and investigated the effects of suppressing RORα by RT-PCR analysis. Results: We showed that suppressing the expression of RORα by the siRNA inhibited the expression of both bone sialoprotein and dentin matrix protein 1. It was discovered coincidentally that the inhibitory effect of RORα resulted in failure of mineralization and bone nodule formation during the course of osteogenesis. Conclusion: The results of this study indicate that RORα must be an imperative modulator of bone sialoprotein and dentin matrix protein 1 involved in osteoblast differentiation and bone formation downstream of Wnt/β-catenin signaling and just prior to the start of mineralization.