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Titolo:
Regulation of cartilage collagenase by doxycycline
Autore:
Shlopov, BV; Stuart, JM; Gumanovskaya, ML; Hasty, KA;
Indirizzi:
Vet Affairs Med Ctr, Memphis, TN 38104 USA Vet Affairs Med Ctr Memphis TNUSA 38104 s Med Ctr, Memphis, TN 38104 USA Univ Tennessee, Dept Med, Dept Anat & Neurobiol, Memphis, TN 38104 USA Univ Tennessee Memphis TN USA 38104 at & Neurobiol, Memphis, TN 38104 USA BD PharMingen, La Jolla, CA USA BD PharMingen La Jolla CA USABD PharMingen, La Jolla, CA USA
Titolo Testata:
JOURNAL OF RHEUMATOLOGY
fascicolo: 4, volume: 28, anno: 2001,
pagine: 835 - 842
SICI:
0315-162X(200104)28:4<835:ROCCBD>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN OSTEOARTHRITIC CARTILAGE; MATRIX-METALLOPROTEINASE INHIBITOR; GROWTH-FACTOR; HUMAN CHONDROCYTES; TETRACYCLINE INHIBITION; COLLAGENOLYTIC ACTIVITY; FIBROBLAST COLLAGENASE; ARTICULAR CHONDROCYTES; SUBSTRATE-SPECIFICITY; GENE-EXPRESSION;
Keywords:
doxycycline; collagenase inhibition; osteoarthritis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Hasty, KA Vet Affairs Med Ctr, 1030 Jefferson Ave, Memphis, TN 38104 USA Vet Affairs Med Ctr 1030 Jefferson Ave Memphis TN USA 38104 USA
Citazione:
B.V. Shlopov et al., "Regulation of cartilage collagenase by doxycycline", J RHEUMATOL, 28(4), 2001, pp. 835-842

Abstract

Objective. To investigate the ability of doxycycline to modulate collagenases, cytokines, and cytokine receptors in chondrocytes from osteoarthritic (OA) cartilage. Methods. Chondrocytes were isolated from human OA cartilage and treated with doxycycline. Synthesis of collagenases, cytokines, and cytokine receptors was quantified by Northern and Western blot analysis and RNase protectionassay. Results, We observed significant inhibition of matrix metalloproteinases (MMP-1) and MMP-13 mRNA and protein production by chondrocytes, isolated from OA cartilage, after treatment with doxycycline. The decrease in collagenase protein level paralleled a decrease in mRNA for these enzymes, suggesting a transcriptional/posttranscriptional level of control. In addition, treatment with 10 mug/ml doxycycline resulted in 2.2-fold upregulation of transforming growth factor (TGF-beta3) and a significant decrease of interleukin1 alpha (IL-1 alpha), IL-1 beta, and IL-6 mRNA. Upregulation of TGF-beta RI and TGF-beta RII was also detected. These cytokines are known to affect collagenase expression and could contribute to inhibition of MMP-1 and MMP-13 production by OA chondrocytes. A decrease in IL-1 alpha, IL-1 beta, acid IL-6 would reduce stimulation of MMP production, while an increase in TGF-beta3 would lead to downregulation of local proinflammatory cytokine production as well as of the collagenases themselves. Conclusion. Our findings show that a decrease in MMP-1 and MMP-13 collagenase production by articular chondrocytes in response to treatment with doxycycline can be explained by a regulatory effect of doxycycline on the production of cytokine and cytokine receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 09:11:43