Hepatocyte growth factor is a coupling factor for osteoclasts and osteoblasts in vitro

Area of Science:

• Cell Biology
• Bone Biology
• Molecular Signaling

Background:

• Hepatocyte growth factor (HGF), also known as scatter factor, is a mesodermal-derived factor influencing epithelial and endothelial cells.
• The c-MET protooncogene encodes the tyrosine kinase receptor for HGF.
• The role of HGF in bone cell regulation was previously unclear.

Purpose of the Study:

• To investigate the expression and function of the HGF receptor (c-MET) in human osteoclasts and osteoblasts.
• To determine the effects of HGF stimulation on these bone cell types.
• To explore the potential autocrine and paracrine roles of HGF in bone.

Main Methods:

• Immunohistochemical analysis of HGF receptor expression in osteoclasts and osteoblasts.
• Stimulation of cell cultures with HGF and measurement of downstream signaling.
• Assays for intracellular calcium, kinase activity (pp60c-Src), cell shape changes, chemotaxis, DNA replication, and DNA synthesis.

Main Results:

• HGF receptor (c-MET) is expressed in human osteoclasts and osteoblasts.
• HGF activates c-MET kinase activity and autophosphorylation in both cell types.
• HGF increases intracellular calcium and activates pp60c-Src in osteoclasts, promoting shape changes, migration, and proliferation.
• HGF stimulates DNA synthesis in osteoblasts, indicating cell cycle entry.
• Osteoclasts synthesize and secrete biologically active HGF.

Conclusions:

• HGF signaling plays a significant role in regulating osteoclast and osteoblast function.
• HGF may exert autocrine control over osteoclasts.
• Osteoclast-derived HGF may paracrinely regulate osteoblasts, suggesting a novel intra-bone signaling loop.