Difference of collagenases regulation in osteoarthritic (OA) chondrocytes

B. V. Shlopov, Karen Hasty

Research output: Contribution to journalArticle

Abstract

We have previously shown that three collagenases, fibroblast collagenase (MMP-1), neutrophil collagenase (MMP-8) and collagenase-3 (MMP-13), are present in normal and OA chondrocytes with distinct up-regulation of all three enzymes in OA cartilage. We have further investigated these enzymes with respect to spatial distribution in OA cartilage and response of the chondrocyte to incubation with different stimuli. We observe increased mRNA for all collagenases in Northern blots of chondrocytes isolated proximal to the observed lesion. Although all collagenases are elevated in OA, the response of the chondrocyte to various growth factors is different. Treatment of OA chondrocytes with transforming growth factor-β (TGFβ) up-regulates MMP-13 and down-regulates MMP-1 and MMP-8. Similarly, MMP-13 shows up-regulation after incubation with retinoic acid (RA) while MMP-1 is down-regulated. Treatment with the proinflammatory factors tumor necrosis factor-α and interleukin- 1-β stimulates all three collagenases. In contrast, incubation with phorbol myristate acetate results in up-regulation of MMP-1 (2.4 - 2.8 fold) and MMP-8 (7.0 -7.6 fold) and down-regulation of MMP-13 (1.6 - 18.9 fold). Thus, the three collagenases synthesized by articular chondrocytes show distinct differences in their pattern of regulation, with MMP-13 showing an additional response to the physiological growth factors, TGFβ and RA, while the other collagenases seem to be regulated strictly by factors elaborated during inflammation. These data suggest a role for MMP-13 in growth and development.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997

Fingerprint

collagenase
chondrocytes
Collagenases
Chondrocytes
Matrix Metalloproteinases
neutrophil collagenase
interstitial collagenase
transforming growth factors
retinoic acid
cartilage
growth factors
Up-Regulation
Matrix Metalloproteinase 8
Cartilage
Transforming Growth Factors
tumor necrosis factors
interleukin-1
Tretinoin
enzymes
matrix metalloproteinase 13

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Difference of collagenases regulation in osteoarthritic (OA) chondrocytes. / Shlopov, B. V.; Hasty, Karen.

In: FASEB Journal, Vol. 11, No. 3, 1997.

Research output: Contribution to journalArticle

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