Molecular Metwork Analysis Of Bone Sialoprotein Promoting Osteoclast Differentiation And Bone Resorption

Background:As populations age and people live longer,osteoporosis is increasingly becoming a global epidemic,affecting more than 200 million people and another severe periodontal disease affects more than 10 percent of adults worldwide,both leading to a reduced quality of life and a huge financial burden.Both diseases are caused by excessive bone resorption.Bone sialoprotein(BSP),a major bone extracellular matrix noncollagenous protein,promotes osteoclast differentiation and bone resorption,but the specific mechanism is stil unclear.Objectives:To identify the BSP-interacting proteins in osteoclasts and determine how BSP interacts with the cells,providing important new insights into the prevention and treatment of osteoporosia,periodontal disease,etc.Methods:BSP was purified by sequential chroma tography on columns of DE-52,TSK gel G3000 SW,and C4 reverse HPLC.It was covalently bound to Dynabeads Dynabeads M-450 Tosylactivated magnetic beads,then incubated with BSP-stimulated RAW264.7(RAW)cells,a macrophage-like cell line.The BSP-interacting proteins were immobilized,purified and analyzed by LC-MS/MS followed by protein-protein interacting network and Gene Ontology and Pathway analyses using STRING database.Results:About100 BSP-interacting proteins were identified.BSP could interacted with type-1 angiotensin II receptor.Conclusions:BSP promotes osteoclast differentiation probably via interacting with type-1angiotensin II receptor.