Orcinol glucoside facilitates the shift of MSC fate to osteoblast and prevents adipogenesis via Wnt/β-catenin signaling pathway.

Background: During osteoporosis, bone mesenchymal stem cells (BMSCs) lineage commitment shifts to adipocytes, causing fat accumulation and bone loss in the skeleton. Seeking drugs that could reverse the adipocyte fate determination of BMSCs is critical for osteoporosis therapy. As a traditional Chinese medicine, Rhizoma Curculiginis (Xianmao) has been used to treat bone diseases and promote bone healing, while the effective constituent of it and the underlying mechanisms are unknown.

Objectives: The aim of this study is to unveil the role of orcinol glucoside (OG), one constituent of Rhizoma Curculiginis, in osteoporosis and BMSCs lineage commitment and to explore the underlying mechanisms.

Methods: Micro-CT and three-point bending test were performed to determine the effect of OG on bone structure and strength. qT-PCR and Western blot were performed to determine the expression of osteogenic or adipogenic differentiation markers in BMSCs. Mineralization in differentiated BMSCs was assessed by Alizarin Red staining, and lipid accumulation in the cells was evaluated by Oil Red O staining. All measurements were performed at least three times.

Results: OG prevented bone loss by stimulating bone formation and attenuating fat formation in bone. In vitro, OG promoted osteoblastic differentiation and inhibited adipogenic differentiation of BMSCs. Inhibition of Wnt/β-catenin by ICG-001 significantly reversed the effect of OG on osteogenic and adipogenic differentiation of BMSCs.

Conclusion: Our study demonstrated the role of OG in alleviating bone loss and fat accumulation in osteoporotic bone, therefore bringing a new therapeutic means to the treatment of osteoporosis.