Inhibition of SFRP1 by microRNA‑206‑3p may be the underlying cause of osteosarcopenia.

Osteosarcopenia is characterized by a simultaneous decrease in bone mass and muscle quality. Thus, determining the common pathogenesis between osteoporosis and sarcopenia may aid in identifying a solution. Secreted frizzled-related protein 1 (SFRP1), a Wnt/β-catenin pathway inhibitor, reportedly decreases during the osteogenesis process and is increased in osteoporosis and sarcopenia mice models. As microRNAs (miRNAs/miRs) can regulate the expression of multiple proteins, the present study aimed to determine if miR-206-3p can promote the nuclear translocation of β-catenin by inhibiting SFRP1 during both osteogenesis and myogenesis. Transcriptome sequencing revealed that SFRP1 was markedly upregulated in the BMSCs derived from ovariectomized mice. In vitro induction of osteogenesis confirmed that SFRP1 negatively regulated osteogenesis. A luciferase reporter assay confirmed that miR-206-3p downregulated SFRP1 by directly binding to the 3' untranslated region. Subsequently, the BMSC and L6 cells were transfected with an miR-206-3p inhibitor or a corresponding negative control. Immunoblotting was performed to assess the relative expression levels of SFRP1 and Wnt/β-catenin signaling. The mRNA levels of SFRP1, osteogenesis-related molecules and myogenesis-related molecules were also detected by quantitative real-time PCR. The miR-206-3p inhibitor reduced the expression of osteogenesis- and myogenesis-related molecules and inactivated the Wnt/β-catenin signaling by releasing SFRP1. In conclusion, miR-206-3p downregulated SFRP1 and activated Wnt/β-catenin signaling to promote osteogenesis and myogenesis. Thus, miR-206-3p may be an important therapeutic target in osteosarcopenia. The present study aimed to uncover the genes and mechanisms that co-regulate muscle and bone. SFRP1, a known regulator of osteoporosis, was examined by analyzing its upstream regulatory microRNA and validating its molecular role. The diagnostic and therapeutic potential of miR-206-3p for osteomyopenia was evaluated by first focusing on osteoporosis and then validating findings with myofibroblasts. These data suggested that miR-206-3p can serve as a therapeutic target for osteomyopenia by inhibiting SFRP1, thereby activating the Wnt/β-catenin signaling pathway and promoting both osteogenesis and myogenesis.