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Osteoactivin inhibition of osteoclastogenesis is mediated through CD44-ERK signaling

Gregory R Sondag1,2, Thomas S Mbimba1,2, Fouad M Moussa1,2

  • 1Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), College of Medicine, Rootstown, OH, USA.

Experimental & Molecular Medicine
|September 3, 2016
PubMed

Insights

Osteoactivin inhibits bone-resorbing osteoclast formation and function. This protein binds CD44, blocking ERK signaling and reducing osteolysis in vivo, revealing a novel pathway for bone remodeling regulation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Bone Biology

Background:

  • Osteoactivin plays a role in bone remodeling.
  • Previous studies show Osteoactivin mutations enhance osteoclast differentiation but inhibit function.
  • The receptor and signaling pathway for Osteoactivin's osteoclast inhibition are uncharacterized.

Purpose of the Study:

  • To investigate Osteoactivin's role in osteoclastogenesis.
  • To identify the signaling pathway involved in Osteoactivin's function.
  • To determine Osteoactivin's effect on receptor activator of nuclear factor-κ B ligand (RANKL)-induced osteolysis in vivo.

Main Methods:

  • Utilized bone marrow-derived osteoclast progenitor cells.
  • Assessed osteoclast differentiation via qPCR, TRAP staining, activity, and cell count.
  • Investigated Osteoactivin binding to CD44 and its effect on ERK phosphorylation.
  • Evaluated Osteoactivin's in vivo efficacy against RANKL-induced osteolysis.

Main Results:

  • Recombinant Osteoactivin inhibited osteoclast differentiation dose-dependently.
  • Osteoactivin was shown to bind CD44 on osteoclasts.
  • Osteoactivin inhibited ERK phosphorylation in a CD44-dependent manner.
  • Osteoactivin treatment inhibited RANKL-induced osteolysis in vivo.

Conclusions:

  • Osteoactivin acts as a negative regulator of osteoclastogenesis both in vitro and in vivo.
  • Osteoactivin exerts its function through binding to CD44 and modulating ERK signaling.
  • This study elucidates a novel mechanism for Osteoactivin in bone remodeling.

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