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Updated: Aug 8, 2026

A RANKL-based Osteoclast Culture Assay of Mouse Bone Marrow to Investigate the Role of mTORC1 in Osteoclast Formation
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Macrophage-stimulating protein (MSP) and its receptor, RON, stimulate human osteoclast activity but not

N Kurihara1, J Tatsumi, F Arai

  • 1Department of Periodontology, Meikai University School of Dentistry, Saitama, Japan.

Experimental Hematology
|October 10, 1998
PubMed

Insights

Macrophage-stimulating protein (MSP) activates the RON receptor, promoting bone resorption by osteoclasts. This pathway is distinct from hepatocyte growth factor (HGF) signaling in osteoclast differentiation.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Bone Biology

Background:

  • Stem cell-derived tyrosine kinase (STK) is part of the hepatocyte growth factor (HGF) receptor family.
  • Macrophage-stimulating protein (MSP) is the ligand for STK and is activated by the coagulation cascade.
  • The RON gene is the human homolog of STK.

Purpose of the Study:

  • To investigate the role of the MSP-RON signaling pathway in human osteoclasts.
  • To determine the effects of MSP and HGF on osteoclast formation and bone resorption.

Main Methods:

  • Detected RON expression in multinucleated osteoclast-like cells (OCLs) using anti-RON antibody.
  • Quantified bone resorption by OCLs on ceramic calcium phosphate films by measuring pit formation.
  • Assessed OCL formation from hematopoietic progenitors and their response to MSP and HGF.

Main Results:

  • RON was expressed in human OCLs.
  • MSP significantly stimulated OCL-mediated bone resorption in a dose-dependent manner.
  • HGF promoted OCL differentiation but did not enhance bone resorption, while MSP stimulated resorption without affecting precursor proliferation.

Conclusions:

  • The MSP-RON signaling pathway plays a crucial role in human osteoclast bone resorption.
  • This function of MSP is distinct from the role of HGF in osteoclast differentiation.
  • The MSP-RON pathway represents a potential target for modulating bone resorption.

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