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Endothelin 1 promotes osteoarthritic cartilage degradation via matrix metalloprotease 1 and matrix metalloprotease 13 induction.
Arthritis Rheum 2003; 48(10):2855-64AR

Abstract

OBJECTIVE

Degradation of the collagenous extracellular matrix by metalloproteases (MMPs) plays an important role in the pathogenesis of osteoarthritis (OA). Recently, it was suggested that endothelin 1 (ET-1), a potent vasoconstrictor, may be involved in MMP regulation. This study investigated the role of ET-1 in OA cartilage degradation.

METHODS

We explored ET-1 expression and synthesis in normal and OA cartilage and synovial membrane by reverse transcription-polymerase chain reaction and immunohistochemistry. MMP-1 and MMP-13 gene expression and protein synthesis were investigated using Northern blotting and enzyme-linked immunosorbent assays. Additionally, ET-1-induced collagenase activity, type II collagen metabolites, and tissue inhibitor of metalloproteases 1 (TIMP-1) protein were evaluated.

RESULTS

We found expression and synthesis of ET-1, in situ, in both normal and OA cartilage and synovial membrane. We demonstrated that ET-1 induced gene expression and protein synthesis of both MMP-1 and MMP-13. These enzymes were produced in OA chondrocyte cultures, and the production increased in a dose-dependent manner in the presence of ET-1. In OA cartilage, ET-1 also induced type II collagen-derived neoepitopes concomitantly with an increase in collagenase activity and a decrease in TIMP-1 protein.

CONCLUSION

Our results provide strong evidence of the catabolic role of ET-1 in OA cartilage via MMP-1 and MMP-13 up-regulation. As well, ET-1 increased the net MMP/TIMP balance and secondarily increased collagen degradation. Hence, ET-1 becomes an attractive factor to target in the conception of new therapeutic approaches for OA and other diseases in which MMP-13 and MMP-1 actions are crucial in tissue alteration.

Authors+Show Affiliations

Osteoarthritis Research Unit, Hôpital Notre-Dame, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

14558091

Citation

Roy-Beaudry, Marjolaine, et al. "Endothelin 1 Promotes Osteoarthritic Cartilage Degradation Via Matrix Metalloprotease 1 and Matrix Metalloprotease 13 Induction." Arthritis and Rheumatism, vol. 48, no. 10, 2003, pp. 2855-64.
Roy-Beaudry M, Martel-Pelletier J, Pelletier JP, et al. Endothelin 1 promotes osteoarthritic cartilage degradation via matrix metalloprotease 1 and matrix metalloprotease 13 induction. Arthritis Rheum. 2003;48(10):2855-64.
Roy-Beaudry, M., Martel-Pelletier, J., Pelletier, J. P., M'Barek, K. N., Christgau, S., Shipkolye, F., & Moldovan, F. (2003). Endothelin 1 promotes osteoarthritic cartilage degradation via matrix metalloprotease 1 and matrix metalloprotease 13 induction. Arthritis and Rheumatism, 48(10), pp. 2855-64.
Roy-Beaudry M, et al. Endothelin 1 Promotes Osteoarthritic Cartilage Degradation Via Matrix Metalloprotease 1 and Matrix Metalloprotease 13 Induction. Arthritis Rheum. 2003;48(10):2855-64. PubMed PMID: 14558091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin 1 promotes osteoarthritic cartilage degradation via matrix metalloprotease 1 and matrix metalloprotease 13 induction. AU - Roy-Beaudry,Marjolaine, AU - Martel-Pelletier,Johanne, AU - Pelletier,Jean-Pierre, AU - M'Barek,Khatija Nait, AU - Christgau,Stephan, AU - Shipkolye,Fazool, AU - Moldovan,Florina, PY - 2003/10/15/pubmed PY - 2003/12/3/medline PY - 2003/10/15/entrez SP - 2855 EP - 64 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 48 IS - 10 N2 - OBJECTIVE: Degradation of the collagenous extracellular matrix by metalloproteases (MMPs) plays an important role in the pathogenesis of osteoarthritis (OA). Recently, it was suggested that endothelin 1 (ET-1), a potent vasoconstrictor, may be involved in MMP regulation. This study investigated the role of ET-1 in OA cartilage degradation. METHODS: We explored ET-1 expression and synthesis in normal and OA cartilage and synovial membrane by reverse transcription-polymerase chain reaction and immunohistochemistry. MMP-1 and MMP-13 gene expression and protein synthesis were investigated using Northern blotting and enzyme-linked immunosorbent assays. Additionally, ET-1-induced collagenase activity, type II collagen metabolites, and tissue inhibitor of metalloproteases 1 (TIMP-1) protein were evaluated. RESULTS: We found expression and synthesis of ET-1, in situ, in both normal and OA cartilage and synovial membrane. We demonstrated that ET-1 induced gene expression and protein synthesis of both MMP-1 and MMP-13. These enzymes were produced in OA chondrocyte cultures, and the production increased in a dose-dependent manner in the presence of ET-1. In OA cartilage, ET-1 also induced type II collagen-derived neoepitopes concomitantly with an increase in collagenase activity and a decrease in TIMP-1 protein. CONCLUSION: Our results provide strong evidence of the catabolic role of ET-1 in OA cartilage via MMP-1 and MMP-13 up-regulation. As well, ET-1 increased the net MMP/TIMP balance and secondarily increased collagen degradation. Hence, ET-1 becomes an attractive factor to target in the conception of new therapeutic approaches for OA and other diseases in which MMP-13 and MMP-1 actions are crucial in tissue alteration. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/14558091/Endothelin_1_promotes_osteoarthritic_cartilage_degradation_via_matrix_metalloprotease_1_and_matrix_metalloprotease_13_induction_ L2 - https://doi.org/10.1002/art.11247 DB - PRIME DP - Unbound Medicine ER -