Proteolysis of Latent Transforming Growth Factor-β (TGF-β)-binding Protein-1 by Osteoclasts A CELLULAR MECHANISM FOR RELEASE OF TGF-β FROM BONE MATRIX

摘要: The binding of growth factors to the extracellular matrix (ECM) may be a key pathway for regulation their activity. We have shown that major mechanism storage transforming factor-beta (TGF-beta) in bone ECM is via its association with latent TGF-beta-binding protein-1 (LTBP1). Although proteolytic cleavage LTBP1 has been reported, it remains unclear whether this represents physiological release matrix-bound TGF-beta. Here we examined role cell-mediated TGF-beta from ECM. first characterized soluble and ECM-bound forms produced by primary osteoblasts. Next, resorbing cells. Isolated avian osteoclasts rabbit marrow-derived released cleavage. 1,25-Dihydroxyvitamin D3 enhanced cleavage, resulting 90% LTBP1. In contrast, osteoblasts failed cleave or Cleavage was inhibited serine protease metalloproteinase (MMP) inhibitors. Studies using purified proteases showed plasmin, elastase, MMP2, MMP9 were able produce 125-165-kDa fragments. These studies identify as novel substrate MMPs provide demonstration proteolysis stores, potentially step which rendered active.