Platelet-Derived Growth Factor BB Secreted From Osteoclasts Acts as an Osteoblastogenesis Inhibitory Factor

• DOI: 10.1359/jbmr.2002.17.2.257
• Publication Date: 2006-04-27T04:16:38Z
• Authors: Kazuishi Kubota; Chisa Sakikawa; Mutsumi Katsumata; Takemichi Nakamura; Kenji Wakabayashi
• Keywords: Platelet-Derived Growth Factor; 0301 basic medicine; Membrane Glycoproteins; Osteoblasts; Receptor Activator of Nuclear Factor-kappa B; Stem Cells; RANK Ligand; Becaplermin; Osteoclasts; Cell Differentiation; Bone Morphogenetic Protein 4; Proto-Oncogene Proteins c-sis; Mice; 03 medical and health sciences; Culture Media, Conditioned; Bone Morphogenetic Proteins; Animals; Carrier Proteins; Cells, Cultured

Osteoclasts and osteoblasts are responsible for strict bone maintenance with a balance between formation resorption by interacting each other. Recently, it has been revealed that osteoblasts/stromal cells regulate differentiation of osteoclasts/hematopoietic two factors, the receptor activator nuclear factor-kappaB (NF-kappaB) ligand (RANKL) on plasma membrane, secreted osteoprotegerin (OPG). However, no factors have yet reported which cells. To elucidate possibility signal transduction from osteoclasts to osteoblasts, we studied conditioned medium mouse osteoclast-like myeloma cell line RAW264.7 treated RANKL. We found this contains factor inhibits osteoblast precursor-like MC3T3-E1 induced morphogenetic protein 4 (BMP-4) named osteoblastogenesis inhibitory (OBIF). OBIF was purified successive three-step chromatography heparin affinity, anion exchange, reversed-phase columns. Osteoblastogenesis activity made one peak in step, showing is single entity. Active fractions were loaded sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) bands proteins excised, digested trypsin, analyzed liquid equipped tandem mass spectrometry (LC/MS/MS). Consequently, identified be platelet-derived growth BB (PDGF BB) homodimer. Furthermore, identification PDGF as confirmed neutralization anti-PDGF antibody. These results show, first time, directly suggest key remodeling.