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Tumor necrosis factor-alpha promotes the expression of osteoprotegerin in rheumatoid synovial fibroblasts.
J Rheumatol. 2004 Mar; 31(3):426-35.JR

Abstract

OBJECTIVE

To clarify the regulation of osteoprotegerin (OPG) expression in rheumatoid synovial fibroblasts by investigating the effect of tumor necrosis factor-alpha (TNF-alpha) and the mechanism of TNF-alpha-induced OPG expression.

METHODS

OPG expression was examined by Northern blot hybridization and reverse transcriptase-polymerase chain reaction in synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and subjects with no inflammatory condition. Amounts of OPG in conditioned medium were determined by ELISA. The effect of OPG on TNF-alpha-induced osteoclastogenesis was investigated in primary cultures of RA synovial cells.

RESULTS

OPG was highly expressed in RA synovial fibroblasts compared to OA and noninflammatory synovial fibroblasts. Different levels of OPG expression were found among patients with RA. TNF-alpha induced OPG expression in all synovial fibroblasts, even OA and noninflammatory fibroblasts, and expression occurred to a remarkable degree in RA fibroblasts. The OPG expression was upregulated by TNF-alpha in a time- and dose-dependent manner. TNF-alpha-induced OPG expression was inhibited by hymenialdisine, a nuclear factor-kappaB inhibitor, in a dose-dependent manner, and expression was inhibited by soluble TNF receptor/Fc fusion protein I (TNFs-RI/Fc), not by TNFs-RII/Fc. In contrast, TNF-alpha-induced osteoclastogenesis in primary cultures of RA synovial cells was inhibited by the addition of OPG.

CONCLUSION

These results suggest that OPG is highly expressed and is upregulated by TNF-alpha in rheumatoid synovial fibroblasts. TNF-alpha-induced OPG expression is mediated predominantly through TNF-RI. Although TNF-alpha is known to stimulate bone destruction, TNF-alpha-induced upregulation of OPG may contribute to self-protection from the bone destruction in RA.

Authors+Show Affiliations

Faculty of Medicine, Toho University, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

14994384

Citation

Kubota, Ayako, et al. "Tumor Necrosis Factor-alpha Promotes the Expression of Osteoprotegerin in Rheumatoid Synovial Fibroblasts." The Journal of Rheumatology, vol. 31, no. 3, 2004, pp. 426-35.
Kubota A, Hasegawa K, Suguro T, et al. Tumor necrosis factor-alpha promotes the expression of osteoprotegerin in rheumatoid synovial fibroblasts. J Rheumatol. 2004;31(3):426-35.
Kubota, A., Hasegawa, K., Suguro, T., & Koshihara, Y. (2004). Tumor necrosis factor-alpha promotes the expression of osteoprotegerin in rheumatoid synovial fibroblasts. The Journal of Rheumatology, 31(3), 426-35.
Kubota A, et al. Tumor Necrosis Factor-alpha Promotes the Expression of Osteoprotegerin in Rheumatoid Synovial Fibroblasts. J Rheumatol. 2004;31(3):426-35. PubMed PMID: 14994384.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor necrosis factor-alpha promotes the expression of osteoprotegerin in rheumatoid synovial fibroblasts. AU - Kubota,Ayako, AU - Hasegawa,Kazuhisa, AU - Suguro,Toru, AU - Koshihara,Yasuko, PY - 2004/3/3/pubmed PY - 2004/6/25/medline PY - 2004/3/3/entrez SP - 426 EP - 35 JF - The Journal of rheumatology JO - J Rheumatol VL - 31 IS - 3 N2 - OBJECTIVE: To clarify the regulation of osteoprotegerin (OPG) expression in rheumatoid synovial fibroblasts by investigating the effect of tumor necrosis factor-alpha (TNF-alpha) and the mechanism of TNF-alpha-induced OPG expression. METHODS: OPG expression was examined by Northern blot hybridization and reverse transcriptase-polymerase chain reaction in synovial fibroblasts from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and subjects with no inflammatory condition. Amounts of OPG in conditioned medium were determined by ELISA. The effect of OPG on TNF-alpha-induced osteoclastogenesis was investigated in primary cultures of RA synovial cells. RESULTS: OPG was highly expressed in RA synovial fibroblasts compared to OA and noninflammatory synovial fibroblasts. Different levels of OPG expression were found among patients with RA. TNF-alpha induced OPG expression in all synovial fibroblasts, even OA and noninflammatory fibroblasts, and expression occurred to a remarkable degree in RA fibroblasts. The OPG expression was upregulated by TNF-alpha in a time- and dose-dependent manner. TNF-alpha-induced OPG expression was inhibited by hymenialdisine, a nuclear factor-kappaB inhibitor, in a dose-dependent manner, and expression was inhibited by soluble TNF receptor/Fc fusion protein I (TNFs-RI/Fc), not by TNFs-RII/Fc. In contrast, TNF-alpha-induced osteoclastogenesis in primary cultures of RA synovial cells was inhibited by the addition of OPG. CONCLUSION: These results suggest that OPG is highly expressed and is upregulated by TNF-alpha in rheumatoid synovial fibroblasts. TNF-alpha-induced OPG expression is mediated predominantly through TNF-RI. Although TNF-alpha is known to stimulate bone destruction, TNF-alpha-induced upregulation of OPG may contribute to self-protection from the bone destruction in RA. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/14994384/Tumor_necrosis_factor_alpha_promotes_the_expression_of_osteoprotegerin_in_rheumatoid_synovial_fibroblasts_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&pmid=14994384 DB - PRIME DP - Unbound Medicine ER -