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The regulation and regulatory role of collagenase in boneInterstitial collagenase plays an important role in both the normal and pathological remodeling of collagenous extracellular matrices, including skeletal tissues. The enzyme is a member of the family of matrix metalloproteinases. Only one rodent interstitial collagenase has been found but there are two human enzymes, human collagenase-1 and -3, the latter being the homologue of the rat enzyme. In developing rat and mouse bone, collagenase is expressed by hypertrophic chondrocytes, osteoblasts, and osteocytes, a situation that is replicated in a fracture callus. Cultured osteoblasts derived from neonatal rat calvariae show greater amounts of collagenase transcripts late in differentiation. These levels can be regulated by parathyroid hormone (PTH), retinoic acid, and insulin-like growth factors, as well as the degree of matrix mineralization. Much of the work on collagenase in bone has been derived from studies on the rat osteosarcoma cell line, UMR 106-01. All bone-resorbing agents stimulate these cells to produce collagenase mRNA and protein, with PTH being the most potent stimulator. Determination of secreted levels of collagenase has been difficult because UMR cells, normal rat osteoblasts, and rat fibroblasts possess a scavenger receptor that removes the enzyme from the extracellular space, internalizes and degrades it, thus imposing another level of control. PTH can also regulate the abundance of the receptor as well as the expression and synthesis of the enzyme. Regulation of the collagenase gene by PTH appears to involve the cAMP pathway as well as a primary response gene, possibly Fos, which then contributes to induction of the collagenase gene. The rat collagenase gene contains an activator protein-1 sequence that is necessary for basal expression, but other promoter regions may also participate in PTH regulation. Thus, there are many levels of regulation of collagenase in bone perhaps constraining what would otherwise be a rampant enzyme.
Document ID
20040173302
Document Type
Reprint (Version printed in journal)
Authors
Partridge, N. C. (Saint Louis University School of Medicine MO 63104, United States)
Walling, H. W.
Bloch, S. R.
Omura, T. H.
Chan, P. T.
Pearman, A. T.
Chou, W. Y.
Date Acquired
August 22, 2013
Publication Date
January 1, 1996
Publication Information
Publication: Critical reviews in eukaryotic gene expression
Volume: 6
Issue: 1
ISSN: 1045-4403
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: AR 39743
CONTRACT_GRANT: DK 47420
CONTRACT_GRANT: AR 40661
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Musculoskeletal
Non-NASA Center
Review
Review, Tutorial