Skip to main content

Advertisement

Log in

IL1-β and TNF-α induce changes in the nuclear polyphosphoinositide signalling system in osteoblasts similar to that occurring in patients with rheumatoid arthritis: an immunochemical and immunocytochemical study

  • Original Paper
  • Published:
Histochemistry and Cell Biology Aims and scope Submit manuscript

Abstract

Osteoarthritis (OA) and rheumatoid arthritis (RA) are common joint diseases that can lead to destruction of cartilage and structural changes in the subchondral bone. In this study we show by western blot and quantitative immunocytochemistry that nuclear phospholipase C β1 (PLCβ1) and phosphatidylinositol 4,5-bisphosphate (PIP2), two key elements of the polyphosphoinositide signal transduction system that regulate different cellular processes, increase in primary osteoblast cultures of RA patients when compared with post-traumatic after fall (PT) patients, whilst those of OA are not significantly affected. Moreover, we demonstrate that these alterations could be induced in PT osteoblasts by proinflammatory cytokines IL-1β and TNF-α. This suggests that proinflammatory cytokines, highly produced by RA infiltrating mononuclear cells, can modulate the nuclear polyphosphoinositide signalling pathway of the osteoblasts involved in bone remodelling.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1a–e.
Fig. 2a–h.
Fig. 3a–g.

Similar content being viewed by others

References

  • Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M (1986) Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 29:1039–1049

    CAS  PubMed  Google Scholar 

  • Arend WP, Dayer JM (1995) Inhibition of the production and effects of interleukin-1 and tumor necrosis factor α in rheumatoid arthritis. Arthritis Rheum 38:151–160

    CAS  PubMed  Google Scholar 

  • Arnett FC, Edworth SM, Bloch DA, et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    CAS  PubMed  Google Scholar 

  • Banfic H, Zizak M, Divecha N, Irvine RF (1993) Nuclear diacylglycerol is increased during cell proliferation in vivo. Biochem J 290:633–636

    CAS  PubMed  Google Scholar 

  • Bodman KB, Roitt IM (1994) The pathophysiology of rheumatoid arthritis. Fundam Clin Immunol 2:73–81

    Google Scholar 

  • Boland CJ, Fried RM, Tashjian AH Jr (1986) Measurement of cytosolic free Ca2+ concentrations in human and rat osteosarcoma cells: actions of bone resorption-stimulating hormones. Endocrinology 118:980–989

    CAS  PubMed  Google Scholar 

  • Bomalaski JS, Clark MA, Douglas SD, Zurier RB (1985) Enhanced phospholipase A2 and C activities of peripheral blood polymorphonuclear leukocytes from patients with rheumatoid arthritis. J Leukoc Biol 38:649–654

    CAS  PubMed  Google Scholar 

  • Divecha N, Banfic H, Irvine RF (1991) The polyphosphoinositide cycle exists in the nuclei of Swiss 3T3 cells under the control of a receptor (for IGF-I) in the plasma membrane, and stimulation of the cycle increases nuclear diacylglycerol and apparently induces translocations of protein kinase C to the nucleus. EMBO J 10:3207–3214

    CAS  PubMed  Google Scholar 

  • Divecha N, Rhee SG, Letcher AJ, Irvine RF (1993) Phosphoinositide signalling enzymes in rat liver nuclei: Phosphoinositidase C isoform β1 is specifically, but not predominantly, located in the nucleus. Biochem J 289:617–620

    CAS  PubMed  Google Scholar 

  • Girasole G, Passeri G, Jilka RL, Manolagas SC (1994) Interleukin-11: a new cytokine critical for osteoclast development. J Clin Invest 93:1516–1524

    PubMed  Google Scholar 

  • Hughes FJ, Howells GL (1993) Interleukin-11 inhibits bone formation in vitro. Calcif Tissue Int 53:362–364

    CAS  PubMed  Google Scholar 

  • Irvine RF (2000) Nuclear lipid signaling. Sci STKE 48:1–12

    Google Scholar 

  • Kuriki H, Tamiya-Koizumi K, Asano M, Yoshida S, Kojima K, Nimura Y (1992) Existence of phosphoinositide-specific phospholipase C in rat liver nuclei and its change during liver regeneration. J Biochem 111:283–286

    CAS  PubMed  Google Scholar 

  • Lisignoli G, Toneguzzi S, Pozzi C, Piacentini A, Riccio M, Ferruzzi A, Gualtieri G, Facchini A (1999) Proinflammatory cytokines and chemokine production and expression by human osteoblasts isolated from patients with rheumatoid arthritis and osteoarthritis. J Rheumatol 26:791–799

    CAS  PubMed  Google Scholar 

  • Lisignoli G, Toneguzzi S, Grassi F, Piacentini A, Tschon M, Cristino Sandra, Gualtieri G, Facchini A (2003) Different chemokines are expressed in human arthritic bone biopsies: IFNγ and IL6 differently modulate IL8, MCP-1 and RANTES production by arthritic osteoblasts. Cytokine 20:231–238

    Article  Google Scholar 

  • Maraldi NM, Zini N, Santi S, Bavelloni A, Valmori A, Marmiroli S, Ognibene A (1993) Phosphoinositidase C isozymes in SaOS-2 cells: immunocytochemical detection in nuclear and cytoplasmic compartments. Biol Cell 79:243–250

    CAS  PubMed  Google Scholar 

  • Maraldi NM, Zini N, Ognibene A, Martelli AM, Barbieri M, Mazzotti G, Manzoli FA (1995) Immunocytochemical detection of the intranuclear variations of phosphatidylinositol 4,5-bisphosphate amount associated with changes of activity and amount of phospholipase C β1 in cells exposed to mitogenic or differentiating agonists. Biol Cell 83:201–210

    Article  CAS  PubMed  Google Scholar 

  • Maraldi NM, Zini N, Santi S, Manzoli FA (1999) Topology of inositol lipid signal transduction in the nucleus. J Cell Physiol 181:203–217

    Article  CAS  PubMed  Google Scholar 

  • Marmiroli S, Ognibene A, Bavelloni A, Cinti C, Cocco L, Maraldi NM (1994) Interleukin 1 α stimulates nuclear phospholipase C in human osteosarcoma SaOS-2 cells. J Biol Chem 269:13–16

    CAS  PubMed  Google Scholar 

  • Martelli AM, Gilmour RS, Bertagnolo V, Neri LM, Manzoli L, Cocco L (1992) Nuclear localization and signalling activity of phosphoinositidase C β in Swiss 3T3 cells. Nature 358:242–245

    Article  CAS  PubMed  Google Scholar 

  • Martelli AM, Billi AM, Manzoli L, Faenza I, Aluigi M, Falconi M, De Pol A, Gilmour RS, Cocco L (2000) Insulin selectively stimulates nuclear phosphoinositide-specific phospholipase C (PI-PLC) β1 activity through a mitogen-activated protein (MAP) kinase-dependent serine phosphorylation. FEBS Lett 486:230–236

    Article  CAS  PubMed  Google Scholar 

  • Mazzoni M, Bertagnolo V, Neri LM, Carini C, Marchisio M, Milani D, Manzoli FA, Capitani S (1992) Discrete subcellular localization of phosphoinositidase C β, γ and δ in PC12 rat pheochromocytoma cells. Biochem Biophys Res Commun 187:114–120

    CAS  PubMed  Google Scholar 

  • Mazzotti G, Zini N, Rizzi E, Rizzoli R, Galanzi A, Ognibene A, Santi S, Matteucci A, Martelli AM, Maraldi NM (1995) Immunocytochemical detection of phosphatidylinositol 4,5-bisphosphate localization sites within the nucleus. J Histochem Cytochem 43:181–191

    CAS  PubMed  Google Scholar 

  • Mino T, Sugiyama E, Taki H, Kuroda A, Yamashita N, Maruyama M, Kobayashi M (1998) Interleukin-1α and tumor necrosis factor α synergistically stimulate prostaglandin E2-dependent production of interleukin-11 in rheumatoid synovial fibroblasts. Arthritis Rheum 41:2004–2013

    Article  CAS  PubMed  Google Scholar 

  • Mohamed-Ali H (1995) Influence of interleukin-1 beta, tumor necrosis factor alpha and prostaglandin E2 on chondrogenesis and cartilage matrix breakdown in vitro. Rheumatol Int 14:191–199

    CAS  PubMed  Google Scholar 

  • Moreland LW, Baumgartner SW, Schiff MH, Tindall EA, Fleischmann RM, Weaver AL, et al (1997) Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. N Engl J Med 337:141–147

    CAS  PubMed  Google Scholar 

  • Piecyk M, Anderson P (2001) Signal transduction in rheumatoid arthritis. Best Pract Res Clin Rheumatol 15:789–803

    Article  CAS  PubMed  Google Scholar 

  • Prestwich GD, Chen R, Feng L, Ozaki S, Ferguson CG, Drees BE, Neklason DA, Mostert MJ, Porter-Gill PA, Kang VH, Shope JC, Neilsen PO, Dewald DB (2002) In situ detection of phospholipid and phosphoinositide metabolism. Adv Enzyme Regul 42:19–38

    Article  CAS  PubMed  Google Scholar 

  • Probert L, Plows D, Kontogeorgos G, Kollias G (1995) The type I interleukin-1 receptor acts in series with tumor necrosis factor (TNF) to induce arthritis in TNF-transgenic mice. Eur J Immunol 25:1794–1797

    CAS  PubMed  Google Scholar 

  • Ridderstad A, Abedi-Valugerdi M, Moller E (1991) Cytokines in rheumatoid arthritis. Ann Med 23:219–223

    CAS  PubMed  Google Scholar 

  • Robey PG, Termine JD (1985) Human bone cells in vitro. Calcif Tissue Int 37:453–460

    CAS  PubMed  Google Scholar 

  • Rodan SB, Wesolowski G, Chin J, Limjuco GA, Schmidt JA, Rodan GA (1990) IL-1 binds to high affinity receptors on human osteosarcoma cells and potentiates prostaglandin E2 stimulation of cAMP production. J Immunol 145:1231–1237

    CAS  PubMed  Google Scholar 

  • Romas E, Udagawa N, Zhou H, Tamura T, Saito M, Taga T, Hilton DJ, Suda T, Ng KW, Martin TJ (1996) The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures. J Exp Med 183:2581–2591

    PubMed  Google Scholar 

  • Santi P, Zini N, Santi S, Riccio M, Guiliani Piccari G, De Pol A, Maraldi NM (2001) Increased activity and nuclear localisation of inositol lipid signal transduction enzymes in rat hepatoma cells. Int J Oncol 18:165–174

    CAS  PubMed  Google Scholar 

  • Satsuma H, Saito N, Hamanishi C, Hashima M, Tanaka S (1996) Alpha and epsilon isozymes of protein kinase C in the chondrocytes in normal and early osteoarthritic articular cartilage. Calcif Tissue Int 58:192–194

    Article  CAS  PubMed  Google Scholar 

  • Sipe JD, Martel-Pelettier J, Otterness IG, Pelettier JP (1994) Cytokine reduction in the treatment of joint conditions. Mediat Inflammation 3:243–256

    CAS  Google Scholar 

  • Toker A (1998) The synthesis and cellular roles of phosphatidylinositol 4,5-bisphosphate. Curr Opin Cell Biol 10:254–261

    CAS  PubMed  Google Scholar 

  • Westacott CI, Webb GR, Warnock MG, Sims JV, Elson CJ (1997) Alteration of cartilage metabolism by cells from osteoarthritic bone. Arthritis Rheum 40:1282–1291

    CAS  PubMed  Google Scholar 

  • Wilder RL (1993) Rheumatoid arthritis. A. Epidemiology, pathology, and pathogenesis. In: Schumacher HR, Klippel JH, Koopman WJ (eds) Primer on the rheumatic diseases. Arthritis Foundation, Atlanta, pp 86–89

  • Woolley DE, Tetlow LC (1997) Observations on the microenvironmental nature of cartilage degradation in rheumatoid arthritis. Ann Rheum Dis 56:151–161

    CAS  PubMed  Google Scholar 

  • Zini N, Martelli AM, Cocco L, Manzoli FA, Maraldi NM (1993) Phosphoinositidase C isoforms are specifically localized in the nuclear matrix and cytoskeleton of Swiss 3T3 cells. Exp Cell Res 208:257–269

    Article  CAS  PubMed  Google Scholar 

  • Zini N, Sabatelli P, Faenza I, Ognibene A, Maraldi NM (1996) Interleukin-1 α induces variations of the intranuclear amount of phosphatidylinositol 4,5-bisphosphate and phospholipase C β1 in human osteosarcoma Saos-2 cells. Histochem J 28:495–504

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Mr. A. Valmori for technical assistance. This work was supported by grants from C.N.R., University of Bologna "Funds for selected research topics", MURST Cofin 2001 and I.O.R. Ricerca Corrente.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nadir Mario Maraldi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zini, N., Lisignoli, G., Solimando, L. et al. IL1-β and TNF-α induce changes in the nuclear polyphosphoinositide signalling system in osteoblasts similar to that occurring in patients with rheumatoid arthritis: an immunochemical and immunocytochemical study. Histochem Cell Biol 120, 243–250 (2003). https://doi.org/10.1007/s00418-003-0563-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00418-003-0563-y

Keywords

Navigation