PiRNA-63049 inhibits bone formation through Wnt/β-catenin signaling pathway

Int J Biol Sci. 2021 Oct 25;17(15):4409-4425. doi: 10.7150/ijbs.64533. eCollection 2021.

Abstract

Bone remodeling is a dynamic process between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Disrupted bone remodeling is a key factor in postmenopausal osteoporosis, a metabolic disorder characterized by deteriorated bone microarchitecture and increased risk of fracture. Recent studies have shown that piwi-binding RNA (piRNA) is involved in the pathogenesis of certain diseases at the post-transcriptional level. Here, we analyzed piRNA-63049 (piR-63049), which may play an essential role in bone remodeling. The expression of piR-63049 significantly increased in both bone tissues and plasma of osteoporotic rats and postmenopausal osteoporotic patients. Overexpressing piR-63049 could inhibit the osteoblastogenesis of bone marrow stromal cells (BMSCs) while knocking down piR-63049 could promote the osteoblastogenesis of BMSCs through the Wnt2b/β-catenin signaling pathway. Moreover, knocking-down piR-63049 (piR-63049-antagonist) in vivo could attenuate the bone loss in ovariectomized rats by promoting bone formation. Taken together, the current study shows that piR-63049 inhibits bone formation through the Wnt2b/β-catenin signaling pathway. This novel piRNA may be a potential target to increase bone formation in bone loss disorders such as postmenopausal osteoporosis.

Keywords: Bone formation; Bone marrow stromal cells; Piwi-interacting RNAs; Wnt signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Bone Density
  • Bone Development / genetics
  • Bone Development / physiology*
  • Bone Marrow Cells
  • Female
  • Gene Expression Regulation / physiology
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Middle Aged
  • Osteogenesis
  • Osteoporosis
  • Ovariectomy
  • RNA, Messenger
  • RNA, Small Interfering
  • Rats
  • Stem Cells
  • Wnt Proteins / genetics
  • Wnt Proteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • Ctnnb1 protein, rat
  • Glycoproteins
  • RNA, Messenger
  • RNA, Small Interfering
  • WNT2B protein, human
  • Wnt Proteins
  • Wnt2b protein, rat
  • beta Catenin