Search

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 [Ca.sup.2+] concentration and by activation of the pp[60.sup.c-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.

Purified recombinant hepatocyte growth factor (HGF) initiates differentiation, growth and colony formation of multipotent and erythroid hemopoietic progenitors. Flow cytometry reveals the presence of the HGF receptor in the cell surface of CD34+ progenitors while the HGF receptor mRNA expression is also detectable in embryonic erythroid cells. HGF also functions as a regulator of paracrine interactions between hemopoietic and stromal cells.