The regulation and regulatory role of collagenase in bone

Nicola Partridge, Hobart W. Walling, Sharon R. Bloch, Terry H. Omura, Prince T. Chan, A. Terrece Pearman, Wan Yin Chou

Research output: Contribution to journalArticle

Abstract

Interstitial 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 we 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.

Original languageEnglish (US)
Pages (from-to)15-27
Number of pages13
JournalCritical Reviews in Eukaryotic Gene Expression
Volume6
Issue number1
StatePublished - 1996

Fingerprint

Collagenases
Bone and Bones
Parathyroid Hormone
Enzymes
Osteoblasts
Matrix Metalloproteinase 1
Matrix Metalloproteinase 13
Genes
fos Genes
Scavenger Receptors
Osteocytes
Transcription Factor AP-1
Bony Callus
Extracellular Space
Somatomedins
Osteosarcoma
Chondrocytes
Tretinoin
Matrix Metalloproteinases
Genetic Promoter Regions

Keywords

  • activator protein-1
  • bone-resorbing hormones
  • differentiated osteoblasts
  • metalloproteinases
  • osteosarcoma
  • parathyroid hormone

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Partridge, N., Walling, H. W., Bloch, S. R., Omura, T. H., Chan, P. T., Pearman, A. T., & Chou, W. Y. (1996). The regulation and regulatory role of collagenase in bone. Critical Reviews in Eukaryotic Gene Expression, 6(1), 15-27.

The regulation and regulatory role of collagenase in bone. / Partridge, Nicola; Walling, Hobart W.; Bloch, Sharon R.; Omura, Terry H.; Chan, Prince T.; Pearman, A. Terrece; Chou, Wan Yin.

In: Critical Reviews in Eukaryotic Gene Expression, Vol. 6, No. 1, 1996, p. 15-27.

Research output: Contribution to journalArticle

Partridge, N, Walling, HW, Bloch, SR, Omura, TH, Chan, PT, Pearman, AT & Chou, WY 1996, 'The regulation and regulatory role of collagenase in bone', Critical Reviews in Eukaryotic Gene Expression, vol. 6, no. 1, pp. 15-27.
Partridge N, Walling HW, Bloch SR, Omura TH, Chan PT, Pearman AT et al. The regulation and regulatory role of collagenase in bone. Critical Reviews in Eukaryotic Gene Expression. 1996;6(1):15-27.
Partridge, Nicola ; Walling, Hobart W. ; Bloch, Sharon R. ; Omura, Terry H. ; Chan, Prince T. ; Pearman, A. Terrece ; Chou, Wan Yin. / The regulation and regulatory role of collagenase in bone. In: Critical Reviews in Eukaryotic Gene Expression. 1996 ; Vol. 6, No. 1. pp. 15-27.
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