Health & Environmental Research Online (HERO)


Print Feedback Export to File
7054610 
Journal Article 
The HGF/Met/NF-kappa B Pathway Regulates RANKL Expression in Osteoblasts and Bone Marrow Stromal Cells 
Tsubaki, M; Nishida, S; Seki, ShI; Takeda, T; Chihara, A; Arai, Y; Morii, Y; Imano, M; Satou, T; Shimomura, K; , 
2020 
Yes 
International Journal of Molecular Sciences
ISSN: 1422-0067
EISSN: 14220067 
MDPI 
BASEL 
33114380 
WOS:000588868200001 
Multiple myeloma (MM)-induced bone disease occurs through hyperactivation of osteoclasts by several factors secreted by MM cells. MM cell-secreted factors induce osteoclast differentiation and activation via direct and indirect actions including enhanced expression of receptor activator of nuclear factor kappa B ligand (RANKL) in osteoblasts and bone marrow stromal cells (BMSCs). Hepatocyte growth factor (HGF) is elevated in MM patients and is associated with MM-induced bone disease, although the mechanism by which HGF promotes bone disease remains unclear. In the present study, we demonstrated that HGF induces RANKL expression in osteoblasts and BMSCs, and investigated the mechanism of induction. We found that HGF and MM cell supernatants induced RANKL expression in ST2 cells, MC3T3-E1 cells, and mouse BMSCs. In addition, HGF increased phosphorylation of Met and nuclear factor kappa B (NF-kappa B) in ST2 cells, MC3T3-E1 cells, or mouse BMSCs. Moreover, Met and NF-kappa B inhibitors suppressed HGF-induced RANKL expression in ST2 cells, MC3T3-E1 cells, and mouse BMSCs. These results indicated that HGF promotes RANKL expression in osteoblasts and BMSCs via the Met/NF-kappa B signaling pathway, and Met and NF-kappa B inhibitors suppressed HGF-induced RANKL expression. Our findings suggest that Met and NF-kappa B inhibitors are potentially useful in mitigating MM-induced bone disease in patients expressing high levels of HGF.