Silencing miR-106b accelerates osteogenesis of mesenchymal stem cells and rescues against glucocorticoid-induced osteoporosis by targeting BMP2

Bone. 2017 Apr:97:130-138. doi: 10.1016/j.bone.2017.01.014. Epub 2017 Jan 17.

Abstract

Osteoporosis is a serious health problem worldwide. MicroRNA is a post-transcriptional regulator of gene expression by either promoting mRNA degradation or interfering with mRNA translation of specific target genes. It plays a significant role in the pathogenesis of osteoporosis. Here, we first demonstrated that miR-106b (miR-106b-5p) negatively regulated osteogenic differentiation of mesenchymal stem cells in vitro. Then, we found that miR-106b expression increased in C57BL/6 mice with glucocorticoid-induced osteoporosis (GIOP), and that silencing of miR-106b signaling protected mice against GIOP through promoting bone formation and inhibiting bone resorption. At last, we showed that miR-106b inhibited osteoblastic differentiation and bone formation partly through directly targeting bone morphogenetic protein 2 (BMP2) both in vitro and in the GIOP model. Together, our findings have identified the role and mechanism of miR-106b in negatively regulating osteogenesis. Inhibition of miR-106b might be a potential new strategy for treating osteoporosis and bone defects.

Keywords: BMP2; Glucocorticoid-induced osteoporosis; Mesenchymal stem cells; Osteogenesis; miR-106b.

MeSH terms

  • Animals
  • Base Sequence
  • Bone Morphogenetic Protein 2 / metabolism
  • Bone Resorption / complications
  • Bone Resorption / pathology
  • Cell Differentiation / radiation effects
  • Dexamethasone / adverse effects
  • Female
  • Gene Knockdown Techniques
  • Gene Silencing* / drug effects
  • Glucocorticoids / adverse effects*
  • Humans
  • Male
  • Mesenchymal Stem Cells / metabolism*
  • Mice, Inbred C57BL
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteogenesis* / drug effects
  • Osteoporosis / chemically induced*
  • Osteoporosis / complications
  • Osteoporosis / genetics*
  • Osteoporosis / pathology
  • Placenta / cytology
  • Pregnancy
  • Smad Proteins / genetics
  • Smad Proteins / metabolism*

Substances

  • Bone Morphogenetic Protein 2
  • Glucocorticoids
  • MicroRNAs
  • Mirn106 microRNA, mouse
  • Smad Proteins
  • Dexamethasone