Decreased microRNA-182-5p helps alendronate promote osteoblast proliferation and differentiation in osteoporosis via

Bao-Long Pan1, Zong-Wu Tong2, Shu-De Li3

  • 1Department of Laboratory, People's Hospital of Yuxi City, Yuxi 653100, P.R. China.

Bioscience Reports
|November 11, 2018
PubMed

Insights

Down-regulated microRNA-182-5p (miR-182-5p) enhances osteoblast activity in osteoporosis by targeting ADCY6 via the Rap1/MAPK pathway. This suggests miR-182-5p as a potential therapeutic target for bone diseases.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Bone Biology

Background:

  • Osteoporosis (OP) is a significant health concern causing bone fragility.
  • MicroRNAs (miRNAs) play crucial roles in bone endocrinology.
  • Understanding miRNA function is vital for developing treatments for bone diseases.

Purpose of the Study:

  • To investigate the role of microRNA-182-5p (miR-182-5p) in osteoblast proliferation and differentiation in alendronate (ALN)-treated osteoporosis (OP) rats.
  • To explore the targeting of adenylyl cyclase isoform 6 (ADCY6) by miR-182-5p and its effect on the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway.

Main Methods:

  • Established rat models of osteoporosis and administered alendronate (ALN) treatment.
  • Quantified expression of miR-182-5p, ADCY6, and Rap1/MAPK pathway genes.
  • Utilized osteoblast transfection with miR-182-5p inhibitor/mimic, si-ADCY6, and U0126 (MAPK inhibitor).
  • Assessed cell proliferation, apoptosis, and differentiation markers (ALP, BGP, COL I).

Main Results:

  • Alendronate (ALN) treatment alleviated osteoporosis symptoms.
  • miR-182-5p was found to negatively target ADCY6, thereby inhibiting the Rap1/MAPK signaling pathway.
  • Down-regulation of miR-182-5p increased osteoblast proliferation and differentiation while reducing apoptosis, evidenced by decreased ALP, BGP, and COL I expression.

Conclusions:

  • Down-regulated miR-182-5p promotes osteoblast proliferation and differentiation in OP rats.
  • This effect is mediated through the activation of the Rap1/MAPK signaling pathway by up-regulating ADCY6.
  • miR-182-5p represents a potential novel therapeutic target for osteoporosis treatment.

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