Linked Life Data

12933685

Source:http://linkedlifedata.com/resource/pubmed/id/12933685

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2003-8-22
pubmed:abstractText
Expression of a constitutively active PTH/PTHrP receptor in cells of osteoblast lineage in vivo (CL2+) causes increases in trabecular bone volume and trabecular bone formation and, conversely, a decrease in the periosteal mineral apposition rate. Collagenase-3 (matrix metalloprotease-13) is a downstream target of PTH action. To investigate the relevance of collagenase cleavage of type I collagen for the CL2+ bone phenotype, we bred CL2+ animals with mice carrying a mutated col1 alpha 1 gene that encodes a protein resistant to digestion by collagenase-3 and other collagenases (rr). Adult tibias and parietal bones from 4-wk-old double-mutant animals (CL2+/rr) and from control littermates were analyzed. Trabecular bone volume was higher in CL2+/rr than in CL2+ mice. This increase occurred despite a modest reduction in bone formation rate, which was, however, still significantly higher that in wild-type littermates, and therefore must reflect decreased bone resorption in rr mice. Osteoclast number was increased in CL2+/rr animals compared with either wild-type or CL2+ mice, suggesting that collagenase-dependent collagen cleavage affected osteoclast function rather than osteoclast number and/or differentiation. Interestingly, the periosteal mineral apposition rate was similar in CL2+/rr and CL2+ animals and was significantly lower than that in wild-type animals. Our study provides evidence that collagenase activity is important for both basal and PTH/PTHrP receptor-dependent osteoclast activation. Furthermore, it indicates that a mild impairment of osteoclast activity is still compatible with increased osteoblast function. Lastly, it supports the hypothesis that collagenases can be a downstream effector of PTH/PTHrP receptor action in trabecular bone, but not in periosteum.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0013-7227
pubmed:author
pubmed:issnType
Print
pubmed:volume
144
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4106-16
pubmed:dateRevised
2011-5-4
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Collagenase cleavage of type I collagen is essential for both basal and parathyroid hormone (PTH)/PTH-related peptide receptor-induced osteoclast activation and has differential effects on discrete bone compartments.
pubmed:affiliation
Cell Biology and Orthopedics, Yale University, New Haven, Connecticut 06520, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.