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Autocrine regulation of collagenase 3 (matrix metalloproteinase 13) during osteoarthritis.
Arthritis Rheum. 2000 Jan; 43(1):195-205.AR

Abstract

OBJECTIVE

To correlate the increased collagenase production previously seen in chondrocytes isolated from osteoarthritic (OA) lesions and the expression of cytokines and cytokine receptors.

METHODS

Chondrocytes were isolated from OA cartilage and characterized for synthesis of collagenases, cytokines, and cytokine receptors by Northern and Western blot analyses, RNA protection assay, and flow cytometry.

RESULTS

Chondrocytes located in cartilage proximal to the macroscopic OA lesions bound more tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) compared with chondrocytes isolated from morphologically normal cartilage from the same joint. In response to TNFalpha stimulation, messenger RNA (mRNA) levels for the IL-1 receptor I (IL-1RI), IL-1RII, TNF receptor II (TNFR II), and IL-6 receptor as well as the level of proinflammatory cytokines, such as IL-1alpha, IL-1beta, lymphotoxin beta, TNFalpha, and IL-6, also increased. In contrast, treatment with transforming growth factor beta1 (TGFbeta1) resulted in down-regulation of matrix metalloproteinase 1 (MMP-1) and MMP-13 concomitant with a reduction in the levels of mRNA for IL-1RI, IL-1RII, TNFRI, and TNFRII and proinflammatory cytokine levels. In contrast, the levels of mRNA for TGFbeta receptor I, TGFbeta1, and TGFbeta3 were up-regulated.

CONCLUSION

These data show that TGFbeta1 has antagonistic effects upon OA chondrocytes, in contrast to the effects seen with TNFalpha. The cyclical course of OA, where a period of active disease is followed by a period of remission, can be explained by a sequential pattern of cytokine stimulation followed by a feedback inhibition of autocrine cytokine production and cytokine receptor expression, thus affecting collagenase synthesis.

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Authors+Show Affiliations

Shlopov BV
Department of Veterans Affairs Medical Center, and University of Tennessee, Memphis 38104, USA.
Gumanovskaya ML
No affiliation info available
Hasty KA
No affiliation info available

MeSH

AgedAutocrine CommunicationChondrocytesCollagenasesFlow CytometryGene Expression Regulation, EnzymologicHumansInterleukin 1 Receptor Antagonist ProteinInterleukin-1Interleukin-10Interleukin-6Matrix Metalloproteinase 1Matrix Metalloproteinase 13Matrix MetalloproteinasesMiddle AgedOsteoarthritisPhenotypeRNA, MessengerReceptors, Interleukin-1Receptors, Interleukin-1 Type IIReceptors, Interleukin-6Receptors, Tumor Necrosis FactorSialoglycoproteinsTransforming Growth Factor betaTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

10643716

Citation

Shlopov, B V., et al. "Autocrine Regulation of Collagenase 3 (matrix Metalloproteinase 13) During Osteoarthritis." Arthritis and Rheumatism, vol. 43, no. 1, 2000, pp. 195-205.
Shlopov BV, Gumanovskaya ML, Hasty KA. Autocrine regulation of collagenase 3 (matrix metalloproteinase 13) during osteoarthritis. Arthritis Rheum. 2000;43(1):195-205.
Shlopov, B. V., Gumanovskaya, M. L., & Hasty, K. A. (2000). Autocrine regulation of collagenase 3 (matrix metalloproteinase 13) during osteoarthritis. Arthritis and Rheumatism, 43(1), 195-205.
Shlopov BV, Gumanovskaya ML, Hasty KA. Autocrine Regulation of Collagenase 3 (matrix Metalloproteinase 13) During Osteoarthritis. Arthritis Rheum. 2000;43(1):195-205. PubMed PMID: 10643716.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autocrine regulation of collagenase 3 (matrix metalloproteinase 13) during osteoarthritis. AU - Shlopov,B V, AU - Gumanovskaya,M L, AU - Hasty,K A, PY - 2000/1/22/pubmed PY - 2000/1/22/medline PY - 2000/1/22/entrez SP - 195 EP - 205 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 43 IS - 1 N2 - OBJECTIVE: To correlate the increased collagenase production previously seen in chondrocytes isolated from osteoarthritic (OA) lesions and the expression of cytokines and cytokine receptors. METHODS: Chondrocytes were isolated from OA cartilage and characterized for synthesis of collagenases, cytokines, and cytokine receptors by Northern and Western blot analyses, RNA protection assay, and flow cytometry. RESULTS: Chondrocytes located in cartilage proximal to the macroscopic OA lesions bound more tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta) compared with chondrocytes isolated from morphologically normal cartilage from the same joint. In response to TNFalpha stimulation, messenger RNA (mRNA) levels for the IL-1 receptor I (IL-1RI), IL-1RII, TNF receptor II (TNFR II), and IL-6 receptor as well as the level of proinflammatory cytokines, such as IL-1alpha, IL-1beta, lymphotoxin beta, TNFalpha, and IL-6, also increased. In contrast, treatment with transforming growth factor beta1 (TGFbeta1) resulted in down-regulation of matrix metalloproteinase 1 (MMP-1) and MMP-13 concomitant with a reduction in the levels of mRNA for IL-1RI, IL-1RII, TNFRI, and TNFRII and proinflammatory cytokine levels. In contrast, the levels of mRNA for TGFbeta receptor I, TGFbeta1, and TGFbeta3 were up-regulated. CONCLUSION: These data show that TGFbeta1 has antagonistic effects upon OA chondrocytes, in contrast to the effects seen with TNFalpha. The cyclical course of OA, where a period of active disease is followed by a period of remission, can be explained by a sequential pattern of cytokine stimulation followed by a feedback inhibition of autocrine cytokine production and cytokine receptor expression, thus affecting collagenase synthesis. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/10643716/Autocrine_regulation_of_collagenase_3__matrix_metalloproteinase_13__during_osteoarthritis_ L2 - https://doi.org/10.1002/1529-0131(200001)43:1<195::AID-ANR24>3.0.CO;2-G DB - PRIME DP - Unbound Medicine ER -