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protein osteoblast mineralization osteoblast differentiation differentiation matrix chapter tissue expression activin figure formation proteome analysis culture bone tissue sample activity bone formation extracellular proteomic peptide process calcification factor actin function effect osteoclast vesicle collagen study score calcium empai growth regulation table number muscle mineral probe binding matrix vesicles mechanism 4 bone samples condition metabolism cell types annexin control development osteoporosis osteoblastic method empai scores empai score alp activity ecm proteins osteogenic period group disease bone metabolism identification differentially phase vehicle change histone cluster medium osteocyte mesenchymal channel result production identi content phosphatase