Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro.
Hepatocyte growth factor (HGF), also known as scatter factor, is a powerful motogen, mitogen, and morphogen produced by cells of mesodermal origin, acting on epithelial and endothelial cells. Its receptor is the tyrosine kinase encoded by the c-MET protooncogene. We show that the HGF receptor is expressed by human primary osteoclasts, by osteoclast-like cell lines, and by osteoblasts. In both cell lineages, HGF stimulation triggers the receptor kinase activity and autophosphorylation. In osteoclasts, HGF receptor activation is followed by increase in intracellular Ca2+ concentration and by activation of the pp60c-Src kinase. HGF induces changes in osteoclast shape and stimulates chemotactic migration and DNA replication. Osteoblasts respond to HGF by entering the cell cycle, as indicated by stimulation of DNA synthesis. Interestingly, osteoclasts were found to synthesize and secrete biologically active HGF. These data strongly suggest the possibility of an autocrine regulation of the osteoclast by HGF and a paracrine regulation of the osteoblast by the HGF produced by the osteoclast.
Grano
M
M
Institute of Human Anatomy, University of Bari Medical School, Italy.
Galimi
F
F
Zambonin
G
G
Colucci
S
S
Cottone
E
E
Zallone
A Z
AZ
Comoglio
P M
PM
D001859:Bone Neoplasms; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004261:DNA Replication / Q000187:drug effects; D004789:Enzyme Activation; D005870:Giant Cell Tumors; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000502:physiology*; D013997:Time Factors
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D016392:Proto-Oncogene Proteins pp60(c-src); D002118:Calcium