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Changes of microRNA profile and microRNA-mRNA regulatory network in bones of ovariectomized mice

Jee Hyun An1, Jung Hun Ohn, Jung Ah Song

  • 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea; Department of Internal Medicine, Konkuk University Medical Center, Seoul, Korea.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|August 10, 2013
PubMed

Insights

MicroRNAs (miRNAs) play a role in bone mass regulation. This study found that miR-127 and miR-136 negatively regulate bone mass in an estrogen-deficient state, offering insights into osteoporosis pathogenesis.

Area of Science:

  • Molecular Biology
  • Genetics
  • Endocrinology

Background:

  • Estrogen deficiency, often due to ovariectomy (OVX), is a primary cause of osteoporosis.
  • MicroRNAs (miRNAs) are increasingly recognized as regulators of bone metabolism.
  • The specific roles of miRNAs in estrogen-deficiency-induced bone loss remain incompletely understood.

Purpose of the Study:

  • To investigate changes in miRNA and mRNA expression profiles in bone tissue following ovariectomy.
  • To elucidate the regulatory mechanisms of bone mass mediated by miRNAs in an estrogen-deficient state.
  • To evaluate the functional roles of specific miRNAs, miR-127 and miR-136, in bone cell differentiation and survival.

Main Methods:

  • Ovariectomy (OVX) and sham operations were performed on mice.
  • Microarray analysis was used to assess miRNA and mRNA expression profiles in bone tissue.
  • Bioinformatic tools predicted miRNA targets and analyzed pathway activation (PPARγ, CREB).
  • In vitro studies involved transfecting cells with miRNA inhibitors and precursors to assess effects on osteoblast and osteocyte differentiation and survival, and osteoclast differentiation.

Main Results:

  • OVX induced significant changes in miRNA expression, with eight upregulated (e.g., miR-127, miR-136) and one downregulated.
  • 658 differentially expressed genes were identified between OVX and sham groups.
  • Integrative analysis suggested activation of PPARγ and CREB pathways.
  • In vitro, miR-127 inhibition enhanced osteoblastic differentiation, while miR-136 precursor inhibited it.
  • Both miR-127 and miR-136 precursors promoted osteoclastic differentiation and aggravated cell death in osteocyte-like cells.

Conclusions:

  • Distinct miRNA expression patterns are associated with estrogen deficiency-induced bone loss.
  • miR-127 and miR-136 negatively regulate bone mass by influencing osteoblast and osteoclast differentiation.
  • These findings highlight a novel miRNA-mRNA regulatory network in the pathogenesis of osteoporosis.
Keywords:
CREBMICROARRAYMICRORNAOSTEOPOROSISOVARIECTOMYPPARγ

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