Open AccessProcollagen C Proteinase Enhancer 1 Genes Are Important Determinants of the Mechanical Properties and Geometry of Bone and the Ultrastructure of Connective Tissues
Author(s) -
Barry M. Steiglitz,
Jaclynn M. Kreider,
Elizabeth P. Frankenburg,
William N. Pappano,
Guy G. Hoffman,
Jeffrey A. Meganck,
Xiaowen Liang,
Magnus Höök,
David E. Birk,
Steven A. Goldstein,
Daniel S. Greenspan
Publication year - 2006
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.26.1.238-249.2006
Subject(s) - biology , ultrastructure , procollagen peptidase , connective tissue , enhancer , anatomy , microbiology and biotechnology , gene , geometry , biophysics , biochemistry , genetics , gene expression , mathematics
Procollagen C proteinases (pCPs) cleave type I to III procollagen C propeptides as a necessary step in assembling the major fibrous components of vertebrate extracellular matrix. The protein PCOLCE1 (p rocol lagenC proteinasee nhancer 1) is not a proteinase but can enhance the activity of pCPs ∼10-fold in vitro and has reported roles in inhibiting other proteinases and in growth control. Here we have generated mice with null alleles of the PCOLCE1 gene,Pcolce , to ascertain in vivo roles. AlthoughPcolce − / − mice are viable and fertile,Pcolce − / − male, but not female, long bones are more massive and have altered geometries that increase resistance to loading, compared to wild type. Mechanical testing indicated inferior material properties ofPcolce − / − male long bone, apparently compensated for by the adaptive changes in bone geometry. Male and femalePcolce − / − vertebrae both appeared to compensate for inferior material properties with thickened and more numerous trabeculae and had a uniquely altered morphology in deposited mineral. Ultrastructurally,Pcolce − / − mice had profoundly abnormal collagen fibrils in both mineralized and nonmineralized tissues. InPcolce − / − tendon, 100% of collagen fibrils had deranged morphologies, indicating marked functional effects in this tissue. Thus, PCOLCE1 is an important determinant of bone mechanical properties and geometry and of collagen fibril morphology in mammals, and the humanPCOLCE1 gene is identified as a candidate for phenotypes with defects in such attributes in humans.