Macrophage-stimulating protein (MSP) and its receptor, RON, stimulate human osteoclast activity but not proliferation: Effect of MSP distinct from that of hepatocyte growth factor

N. Kurihara, J. Tatsumi, F. Arai, A. Iwama, T. Suda

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Stem cell-derived tyrosine kinase (STK) is a member of the hepatocyte growth factor (HGF) receptor family. The ligand for STK, macrophage- stimulating protein (MSP), is a serum protein activated by members of the coagulation cascade. The RON gene is a human homolog of the murine STK. In this study we examined the role of MSP-RON in the signal pathway of human osteoclasts. Using anti-RON antibody, we detected RON expressed in multinucleated osteoclast-like cells (OCLs) formed in cultures of human bone marrow cells. To determine bone resorption, we placed OCLs on thin films of ceramic calcium phosphate formed on quartz plate-coated slides (Millenium Biologix) and measured pit formation. MSP stimulated pit formation by OCLs in a dose-dependent manner. MSP (50 ng/mL) caused a fourfold increase in pit area compared with the control. Furthermore, we examined the effects of MSP and HGF on OCL formation by purified populations of hematopoietic progenitors. OCLs were phenotypically identified by their cross-reactivity with 23c6, a monoclonal antibody that preferentially binds to osteoclasts. HGF (50 ng/mL) stimulated the differentiation of progenitors to 23c6-positive OCLs but did not enhance bone absorption. In contrast, MSP did not affect proliferation of osteoclast precursors but stimulated bone resorption by OCLs. We conclude that the MSP signal transduction pathway plays a role in bone resorption that is distinct from that of HGF.

Original languageEnglish
Pages (from-to)1080-1085
Number of pages6
JournalExperimental Hematology
Volume26
Issue number11
Publication statusPublished - 1998 Oct 29

Keywords

  • Bone resorption
  • Macrophage-stimulating protein
  • Osteoclasts
  • RON

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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