Abstract
Interleukin-1 (IL-1) and tumor necrosis factor (TNF), two pleiotropic cytokines produced in inflammatory processes, inhibit bone matrix biosynthesis and stimulate prostanoid formation in osteoblasts. In the present study, the importance of prostaglandin formation in IL-1 and TNF-induced inhibition of osteocalcin and type I collagen formation has been examined. In the human osteoblastic cell line MG-63, IL-1α (10–1000 pg/ml), IL-1β (3–300 pg/ml) and TNF-α (1–30 ng/ml) stimulated prostaglandin E2 (PGE2) formation and inhibited, 1,25(OH)2-vitamin D3-induced osteocalcin biosynthesis as well as basal production of type I collagen. Addition of PGE2 or increasing the endogenous formation of PGE2 by treating the cells with arachidonic acid, bradykinin, Lys-bradykinin or des-Arg9-bradykinin, did not affect osteocalcin and type I collagen formation in unstimulated or 1,25(OH)2-vitamin D3-stimulated osteoblasts. Four non-steroidal anti-inflammatory drugs, indomethacin, flurbiprofen, naproxen and meclofenamic acid, inhibited basal, IL-1 β- and TNF-α-stimulated PGE2 formation in the MG-63 cells without affecting IL-1 β- or TNF-α-induced inhibition of osteocalcin and type I collagen formation. In isolated, non-transformed, human osteoblast-like cells, IL-1 β and TNF-α stimulated PGE2 formation and concomitantly inhibited 1,25(OH)2-vitamin D3-stimulated osteocalcin biosynthesis, without affecting type I collagen formation. In these cells, indomethacin and flurbiprofen abolished the effects of IL-1 β and TNF-α on prostaglandin formation without affecting the inhibitory effects of the cytokines on osteocalcin biosynthesis. These data show that IL-1 and TNF inhibit osteocalcin and type I collagen formation in osteoblasts independently of prostaglandin biosynthesis and that non-steroidal antiinflammatory drugs do not affect the effects of IL-1 and TNF on bone matrix biosynthesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Evans DB, Thavarajah M, Kanis JA. Involvement of prostaglandin E2 in the inhibition of osteocalcin synthesis by human osteoblast-like cells in response to cytokines and systemic hormones. Biochem Biophys Res Commun 1990;167:194–20.
Li YP, Stashenko P. Proinflammatory cytokines tumor necrosis factor-α and IL-6, but not IL-1, downregulate the osteocalcin gene promotor. J Immunol 1992;148:788–94.
Taichman RS, Hauschka PV. Effects of interleukin-1β and tumor necrosis factor-α on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro. Inflammation 1992;16:587–601.
Canalis E. Effects of tumor necrosis factor on bone formation in vitro. Endocrinology 1987;121:1596–604.
Centrella M, McCarthy TL, Canalis E. Tumor necrosis factor-α inhibits collagen synthesis and alkaline phosphatase activity independently of its effect on deoxyribonucleic acid synthesis in osteoblast-enriched bone cell cultures. Endocrinology 1988;123:1442–8.
Nanes MS, McKoy WM, Marx SJ. Inhibitory effects of tumor necrosis factor-α and interferon-γ on deoxyribonucleic acid and collagen synthesis by rat osteosarcoma cells (ROS 17/2.8). Endocrinology 1989;124:339–45.
Bertolini DR, Nedwin GE, Bringman TS, Smith DD, Mundy GR. Stimulation of bone resorption and inhibition of bone formation in vitro by human tumor necrosis factors. Nature 1986;319:516–8.
Stashenko P, Dewhirst FE, Rooney ML, Desjardins LA, Heeley J. Interleukin 1β is a potent inhibitor of bone formation in vitro. J Bone Min Res 1987;2:559–65.
Nguyen L, Dewhirst FE, Hauschka PV, Stashenko P. Interleukin-1β stimulates bone resorption and inhibits bone formation in vivo. Lymph Cytok Res 1991;10:15–21.
Gowen M. Interleukin 1 and tumor necrosis factor. In: Gowen M, editor. Cytokines and Bone Metabolism. Boca Raton: CRC Press, 1992:71–91.
Clover I, Gowen M. Are MG-63 and HOS TE85 human osteosarcoma cell lines representative models of the osteoblastic phenotype? Bone 1994;15:585–91.
MacDonald BR, Gallagher JA, Rusell RGG. Parathyroid hormone stimulates the proliferation of cells derived from human bone. Endocrinology 1986;118:2445–9.
Hauschka PV, Lian JB, Cole DE, Grundberg CM. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 1989;69:990–1047.
Termine JD. Bone matrix proteins and the mineralization process. In: Favus MJ, editor. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 2nd ed. New York: Raven Press, 1993:21–5.
Lerner UH. Effects of kinins, thrombin and neuropeptides on bone. In: Gowen M, editor. Cytokines and Bone Metabolism. Boca Raton: CRC Press, 1992:267–98.
Lerner UH. Regulation of bone metabolism by the kallikreinkinin system, the coagulation cascade, and the acute-phase reactants. Oral Surg Oral med Oral Pathol 1994;7:481–93.
Lerner UH, Ohlin A. Tumor necrosis factors α and β can stimulate bone resorption in cultured mouse calvariae by a prostaglandin-independent mechanism. J Bone Min Res 1993;8:147–55.
Lerner UH, Ljunggren Ö, Dewhirst FE, Boraschi D. Comparison of human interleukin-1β and its 163–171 peptide in bone resorption and the immune response. Cytokine 1991;3:141–8.
Author information
Authors and Affiliations
Additional information
accepted by W. B. van den Berg
Rights and permissions
About this article
Cite this article
Rosenquist, J.B., Ohlin, A. & Lerner, U.H. Cytokine-induced inhibition of bone matrix proteins is not mediated by prostaglandins. Inflamm Res 45, 457–463 (1996). https://doi.org/10.1007/BF02252317
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02252317