title: A procollagen C-proteinase inhibitor diminishes collagen and lysyl oxidase processing but not collagen cross-linking in osteoblastic cultures.
abstract: The deposition of insoluble functional collagen occurs following extracellular proteolytic processing of procollagens by procollagen N- and C-proteinases, fibril formation, and lysyl oxidase dependent cross-linking. Procollagen C-proteinases in addition process and activate lysyl oxidase. The present study evaluates a possible role for procollagen C-proteinases in controlling different aspects of collagen deposition in vitro. Studies determine whether inhibition of procollagen C-proteinase activity with a specific BMP-1 inhibitor results in perturbations in lysyl oxidase activation, and in collagen processing, deposition, and cross-linking in phenotypically normal cultured murine MC3T3-E1 cells. Data show that BMP-1 Inhibitor dose dependently inhibits lysyl oxidase activation by up to 50% in undifferentiated proliferating cells. In differentiating cultures, BMP-1 inhibitor decreased collagen processing but did not inhibit the accumulation of mature collagen cross-links. Finally, electron microscopy studies show that collagen fibril diameter increased. Thus, inhibition of procollagen C-proteinases results in perturbed collagen deposition primarily via decreased collagen processing.
authors.affiliation: Division of Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, MA 02118, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Pischon
authors.forename: Hermik
authors.initials: H
authors.lastname: Babakhanlou-Chase
authors.forename: Laurent
authors.initials: L
authors.lastname: Darbois
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Ho
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Brenner
authors.forename: Efrat
authors.initials: E
authors.lastname: Kessler
authors.forename: Amitha H
authors.initials: AH
authors.lastname: Palamakumbura
authors.forename: Philip C
authors.initials: PC
authors.lastname: Trackman
mesh_terms: D000818:Animals; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000378:metabolism; D004347:Drug Interactions; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D011499:Protein Processing, Post-Translational; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D003432:Cross-Linking Reagents; D006877:Hydroxamic Acids; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D008249:Protein-Lysine 6-Oxidase; D008666:Metalloendopeptidases; C525707:Bmp1 protein, mouse; D055395:Bone Morphogenetic Protein 1