A procollagen C-proteinase inhibitor diminishes collagen and lysyl oxidase processing but not collagen cross-linking in osteoblastic cultures

Nicole Pischon, Hermik Babakhanlou-Chase, Laurent Darbois, Wen Bin Ho, Mitchell C. Brenner, Efrat Kessler, Amitha H. Palamakumbura, Philip C. Trackman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)111-117
Number of pages7
JournalJournal of Cellular Physiology
Volume203
Issue number1
DOIs
StatePublished - Apr 2005

Funding

FundersFunder number
National Institute of Dental and Craniofacial ResearchR01DE014066

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