HGF Inhibits BMP-Induced Osteoblastogenesis: Implications for the Bone Disease in Multiple Myeloma.

Multiple myeloma is a hematological malignancy characterized by accumulation of malignant plasma cells in the bone marrow. Most patients develop osteolytic lesions, caused by an uncoupling of bone formation from bone resorption. In patients with osteolytic lesions the osteoblasts are fewer and less active. HGF (Hepatocyte Growth Factor) is produced by the malignant plasma cells and is found at high concentrations in the bone marrow of most patients with multiple myeloma. In this study we show that HGF inhibited BMP-induced expression of alkaline phosphatase and mineralization in human mesenchymal stem cells (MSC) and the murine myoid cell line C2C12. Furthermore, the expression of the osteoblast-specific transcription factors Runx2 and Osterix was reduced by HGF treatment. HGF inhibited BMP-induced differentiation of MSC partly by keeping the cells in a proliferative, undifferentiated state. The in vitro data was supported by the observation of a negative correlation between HGF and a marker of osteoblast activity, bone specific alkaline phosphatase (rho=−0,45, p=0,008), in sera from 34 myeloma patients. These observations suggest that HGF inhibits bone formation in multiple myeloma.