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Decreased SH3BP2 inhibits osteoclast differentiation and function

Teruya Kawamoto1, Chun Fan, Robert J Gaivin

  • 1Department of Anatomic Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
|March 31, 2011
PubMed

Insights

Decreasing SH3BP2 levels inhibits osteoclast differentiation and function, crucial for bone remodeling. This finding highlights SH3BP2 as a potential target for managing excessive bone resorption disorders.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Skeletal Biology

Background:

  • Germline mutations in the SH3BP2 gene are linked to cherubism, a skeletal disorder.
  • Cherubism involves excessive osteoclastic bone resorption in the jawbone.
  • Previous work showed SH3BP2 overexpression enhances osteoclast formation.

Purpose of the Study:

  • To investigate the impact of reduced SH3BP2 levels on osteoclastogenesis.
  • To determine the role of SH3BP2 in regulating osteoclast differentiation and function.

Main Methods:

  • Utilized shRNA to knock down SH3BP2 expression in cells.
  • Examined downstream signaling pathways, including PLCγ2 phosphorylation and NFATc1 expression.
  • Assessed osteoclast differentiation, multinucleation, and bone resorptive activity in vitro.
  • Analyzed osteoclast formation in Sh3bp2(-/-) deficient mice.

Main Results:

  • SH3BP2 knockdown reduced PLCγ2 phosphorylation and NFATc1 expression.
  • Knockdown led to decreased expression of osteoclast-specific genes.
  • Fewer and smaller TRAP-positive multinucleated osteoclasts were formed upon SH3BP2 reduction.
  • Bone resorption activity was significantly inhibited by SH3BP2 knockdown.
  • Osteoclasts from Sh3bp2(-/-) mice were smaller and stained less intensely for TRAP.

Conclusions:

  • SH3BP2 plays a critical role in promoting osteoclast differentiation and function.
  • Reduced SH3BP2 levels significantly impair osteoclastogenesis.
  • SH3BP2 is a potential therapeutic target for suppressing pathological bone resorption.

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