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. <i>In vitro</i> 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.