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FBXO11 regulates bone development

Hong Huang1, Jianrong Lu2, Ikramuddin Aukhil1

  • 1Department of Periodontology, University of Florida, Gainesville, FL 32610, USA.

Bone
|March 2, 2023
PubMed

Insights

FBXO11 regulates bone development by controlling osteoblast differentiation. Its deficiency leads to Snail1 accumulation, inhibiting bone formation and mineralization.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Developmental Biology

Background:

  • FBXO11 is a key component of the SKP1-cullin-F-boxes ubiquitin ligase complex.
  • The function of FBXO11 in bone development remains largely unknown.

Purpose of the Study:

  • To elucidate the role of FBXO11 in regulating osteogenic differentiation and bone development.
  • To investigate the molecular mechanism by which FBXO11 influences bone formation.

Main Methods:

  • FBXO11 gene knockdown and overexpression in mouse pre-osteoblast MC3T3-E1 cells.
  • Generation of osteoblastic-specific FBXO11 conditional knockout mouse models (Col1a1-ERT2-FBXO11KO and Bglap2-FBXO11KO).
  • Analysis of osteogenic and osteoclastic activity, Snail1 protein ubiquitination, and bone mineralization.

Main Results:

  • FBXO11 knockdown reduced osteogenic differentiation; overexpression accelerated it in vitro.
  • FBXO11 deficiency in conditional knockout mice inhibited bone growth with reduced osteogenic activity.
  • FBXO11 deficiency caused Snail1 protein accumulation in osteoblasts by reducing its ubiquitination, suppressing osteogenic activity and bone mineralization.

Conclusions:

  • FBXO11 plays a critical role in regulating osteoblast differentiation and bone formation.
  • FBXO11 deficiency inhibits bone development by promoting Snail1 accumulation, which impairs osteogenic activity and mineralization.
Keywords:
Bone formationFBXO11OsteoblastSnail1

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