Inhibition of miR-29 Activity in the Myeloid Lineage Increases Response to Calcitonin and Trabecular Bone Volume in

Bongjin Shin1,2, Henry C Hrdlicka3, Anne M Delany3

  • 1Center on Aging, UConn Health, Farmington, CT 06030, USA.

Endocrinology
|June 30, 2021
PubMed

Insights

Inhibition of miR-29-3p microRNAs in myeloid cells enhances bone volume by reducing bone resorption. This study reveals miR-29-3p

Area of Science:

  • Molecular Biology
  • Bone Biology
  • MicroRNA Therapeutics

Background:

  • MicroRNAs (miRNAs) regulate cellular processes, including bone metabolism.
  • The miR-29-3p family is implicated in osteoclastogenesis, the process of bone resorption.
  • Understanding miRNA roles is crucial for developing bone disease treatments.

Purpose of the Study:

  • To investigate the role of miR-29-3p in bone homeostasis and osteoclast function.
  • To explore the therapeutic potential of inhibiting miR-29-3p in vivo.
  • To elucidate the molecular mechanisms linking miR-29-3p to bone resorption.

Main Methods:

  • Development of a novel knockin tough decoy mouse model to inhibit miR-29-3p in myeloid cells.
  • Analysis of bone volume (trabecular and cortical) and bone resorption markers in vivo.
  • In vitro studies using osteoclasts to assess the impact of miR-29-3p inhibition on calcitonin receptor (Calcr) and cathepsin K (Ctsk) expression and function.

Main Results:

  • Inhibition of miR-29-3p in myeloid lineage cells led to increased trabecular and cortical bone volume due to decreased bone resorption.
  • miR-29-3p inhibition upregulated Calcitonin receptor (Calcr) expression, enhancing osteoclast responsiveness to calcitonin.
  • Cathepsin K (Ctsk) levels were decreased in miR-29-3p inhibited osteoclasts, with Calcr knockdown restoring Ctsk levels, indicating a Calcr-cAMP-Ctsk pathway modulated by miR-29-3p.

Conclusions:

  • miR-29-3p promotes bone resorption during RANKL-induced osteoclastogenesis and normal bone remodeling.
  • Inhibiting miR-29-3p in the myeloid lineage offers a potential therapeutic strategy for increasing bone mass.
  • This study establishes a novel link between miR-29-3p, Calcr, and Ctsk in regulating osteoclastic bone resorption and bone homeostasis.

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