miR-26b modulates OA induced BMSC osteogenesis through regulating GSK3ß/ß-catenin pathway.

ABSTRACT

BACKGROUNDS Osteoactivin (OA) is a key regulator promoting bone marrow stromal cells osteogenesis progress, while Dexamethasone (Dex) could inhibit OA induced osteogenesis and lead to osteoporosis. miR-26b increased during BMSC osteogenesis but whether it participates in this progress is enigma. Osteogenesis is under regulation of canonical Wnt signaling pathway which could serve as potential target for miR-26b. It bears therapeutic potential if miR-26b could regulate osteogenesis and antagonize Dex induced Osteoporosis (OP). METHODS: BMSC were isolated from bone marrow of rats and induced for osteogenesis by OA administration. We detected miR-26b mRNA level together with osteogenesis related genes or Wnt signal pathway related genes by qRT-PCR. BMSC cells with miR-26b inhibitor or mimics revealed the effect of miR-26b on osteogenesis. The osteogenesis efficiency was detected by Alizarin Red staining and ALP activity. Protein level of canonical Wnt signal pathway and other proteins were detected by Western blot. The interaction between miR-26b and GSK3ß was detected by dual luciferase reporter assay. RESULTS: We found that miR-26b was increased during OA induced BMSC osteogenesis. Inhibiting miR-26b could lead to osteogenesis inhibition while miR-26b mimics could promote this progress. The key regulator of Wnt signal pathway GSK3ß is down-regulated when miR-26b was overexpressed, resulting in ß-catenin activation. Since Dex could promote GSK3ß expression and inhibit Wnt signal, miR-26b could also alleviate Dex induced osteogenesis inhibition. CONCLUSION: Our findings indicate that miR-26b promoted BMSC osteogenesis by directly targeting GSK3ß and activating canonical Wnt signal pathway, suggesting miR-26b might be serve as potential therapeutic candidate of osteoporosis.