Biogerontology

, 4:309 | Cite as

Age-associated changes in functional response to CXCR3 and CXCR5 chemokine receptors in human osteoblasts

  • Gina Lisignoli
  • Anna Piacentini
  • Stefania Toneguzzi
  • Francesco Grassi
  • Matilde Tschon
  • Sandra Cristino
  • Andrea Facchini
  • Erminia Mariani
Article

Abstract

The expression and functional activity of CXC chemokine receptors were evaluated in human osteoblasts (OB) obtained post-trauma from old donors compared to very young donors. It was found that CXCR1 and CXCR4 were only expressed by old but not young donors' cells. In contrast, CXCR3 and CXCR5 were expressed by both young and old donors. We functionally evaluated CXCR3/CXCL10 and CXCR5/CXCL13 receptor/ligand pairs by analysing cell proliferation and the release of N-acetyl-β-D-glucosaminidase (NAG), an enzyme that degrades glycosaminoglycans and hyaluronic acid. CXCL10 and CXCL13 induced a dose-dependent increase of cell proliferation in OB from young donors while cell proliferation of OB in old donors was not affected. By contrast, CXCL10 and CXCL13 induced a significantly higher NAG release in OB from old donors compared to young ones. These data demonstrate a significant age-dependent difference in the response of OB to CXCL10 and CXCL13 stimulation. These chemokines induce an inverse response of OB from old and young donors, which suggests a role of ageing in the modulation of cellular response of bone cells.

ageing alkaline phosphatase chemokine osteoblasts proliferation 

References

  1. Blanco FJ, Geng Y and Lotz M (1995) Differentiation-dependent effects of IL-1 and TGF-? on human articular chondrocyte proliferation are related to inducible nitric oxide synthase expression. J Immunol 154: 4018-4026PubMedGoogle Scholar
  2. Bodo M, Carinci P, Venti G, Giammarioli M, Donti E, Stabellini G, Paludetti G and Becchetti E (1997) Glycosaminoglycan metabolism and cytokine release in normal and osteosclerotic human bone cells interleukin-1 treated. Conn Tissue Res 36: 231-240CrossRefGoogle Scholar
  3. Chan GK and Duque G (2002) Age-related bone loss: old bone, new facts. Gerontology 48: 62-71PubMedCrossRefGoogle Scholar
  4. Curnock AP, Logan MK and Ward SG (2002) Chemokine signalling: pivoting around multiple phosphoinositide 3-kinases. Immunology 105: 125-136PubMedCrossRefGoogle Scholar
  5. D'Ippolito G, Schiller PC, Ricordi C, Roos BA and Howard GA (1999) Age-related osteogenic potential of mesenchymal stromal stem cells from human vertebral bone marrow. J Bone Miner Res 14: 1115-1122PubMedCrossRefGoogle Scholar
  6. Del Pozo M, Vicente-Manzanares M, Tejedor R, Serrador JM and Sanchez-Madrid F (1999) Rho GTPases control migration and polarisation of adhesion molecules and cytoskeletal ERM components in T lymphocytes. Eur J Immunol 29: 3609-3620PubMedCrossRefGoogle Scholar
  7. Ducy P, Schinke T and Karsenty G (2000) The osteoblast: a sophisticated fibroblast under central surveillance. Science 289: 1501-1504PubMedCrossRefGoogle Scholar
  8. Fedarko NS, Bianco P, Vetter U and Robey Gehron P (1990) Human bone cell enzyme expression and cellular heterogeneity: correlation of alkaline phosphatase enzyme activity with cell cycle. J Cell Physiol 144: 115-121PubMedCrossRefGoogle Scholar
  9. Frade JM, Mellado M, Lind P, Gutierrez-Ramos JC and Martínez-A. C (1997) Characterization of the CCR2 chemokine receptor. Functional CCR2 receptor expression on B cells. J Immunol 159: 5576-5584PubMedGoogle Scholar
  10. Gamble JG, Haimson R and Smith RL (1990) Glucosaminidase, galactosaminidase, and glucuronidase in the growth plate. J Orthop Res 8: 764-768PubMedCrossRefGoogle Scholar
  11. Graves DT, Jiang Y and Valente AJ (1999) The expression of monocyte chemoattractant protein-1 and other chemokines by osteoblasts. Front Biosci 4: D571-D580PubMedGoogle Scholar
  12. Klippel A, Escobedo MA, Wachowicz MS, Apell G, Brown TW, Giedlin MA, Kavanaugh WM and Williams LT (1998) Activation of phosphatidylinositol 3-kinase is sufficienf for cell cycle entry and promotes cellular changes characteristic of oncogenic transformation. Mol Cell Biol 18: 5699-5711PubMedGoogle Scholar
  13. Kveiborg M, Rattan SIS, Clark BFC, Eriksen EF and Kassem M (2001) Treatment with 1,25-dihydroxyvitamin D3 reduces impairment of human osteoblast functions during cellular aging in culture. J Cell Physiol 186: 298-306PubMedCrossRefGoogle Scholar
  14. Lisignoli G, Toneguzzi S, Pozzi C, Piacentini A, Riccio M, Ferruzzi A, Gualtieri G and Facchini A (1999) Proinflammatory cytokines and chemokine production and expression by human osteoblasts isolated from patients with rheumatoid arthritis and osteoarthritis. J Rheumatol 26: 791-799PubMedGoogle Scholar
  15. Lisignoli G, Piacentini A, Toneguzzi S, Grassi F, Cocchini B, Ferruzzi A, Gualtieri G and Facchini A (2000) Osteoblasts and stromal cells isolated from femora in rheumatoid arthritis (RA) and osteoarthritis (OA) patients express IL-11, leukemia inhibitory factor and oncostatin M. Clin Exp Immunol 119: 346-353PubMedCrossRefGoogle Scholar
  16. Lisignoli G, Toneguzzi S, Piacentini A, Cattini L, Lenti A, Tschon M, Cristino S, Grassi F, Facchini A (2003) Human osteoblasts express functional CXC Chemokine receptors 3 and 5: activation by their ligands CXCL10 and CXCL13, significantly induce alkaline phosphatase and ?-N-acetylhexosaminidase release. J Cell Physiol 194: 71-79PubMedCrossRefGoogle Scholar
  17. Mackay CR (2001) Chemokines: immunology's high impact factors. Nature Immunol 2: 95-101CrossRefGoogle Scholar
  18. Marks SC and Odgren PR (2002) In: Bilezikian JP Raisz LG and Rodan GA (eds) Structure and Development of the Skeleton: Principles of Bone Biology, pp 3-15. Academic Press, San Diego, CaliforniaGoogle Scholar
  19. Martínez P, Moreno I, De Miguel F, Vila V, Esbrit P and Martínez ME (2001) Changes in osteocalcin response to 1,25-dihydroxyvitamin D3, stimulation and basal vitamin D receptor expression in human osteoblastic cells according to donor age and skeletal origin. Bone 29: 35-41PubMedCrossRefGoogle Scholar
  20. Mellado M, Rodríguez-Frade JM, Mañez S and Martínez-A. C (2001) Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation. Annu Rev Immunol 19: 397-421PubMedCrossRefGoogle Scholar
  21. Moelling K, Schad K, Bosse M, Zimmermann S and Schweneker M (2002) Regulation of Raf-Akt Cross-talk. J Biol Chem 277: 31099-31106PubMedCrossRefGoogle Scholar
  22. Moser B and Loetscher P (2001) Lymphocyte traffic control by chemokines. Nature Immunol 2: 123-128CrossRefGoogle Scholar
  23. Murphy PM (1994) The molecular biology of leukocyte chemoattractant receptors. Annu Rev Immunol 12: 593-633PubMedCrossRefGoogle Scholar
  24. Murphy PM, Baggiolini M, Charo IF, Hebert CA, Horuk R, Matsushima K, Miller LH, Oppenheim JJ and Power CA (2000) International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 52: 145-176PubMedGoogle Scholar
  25. Nefussi JR, Pouchelet M, Collin P, Sautier JM, Develay G and Forest N (1989) Microcinematographic and autoradiographic kinetic studies of bone cell differentiation in vitro: matrix formation and mineralization. Bone 10: 345-352PubMedCrossRefGoogle Scholar
  26. Paoletti S, Borzì RM, Mazzetti I, Magagnoli G, Macor S, Cattini L and Facchini A (2001) Human osteosarcoma cells release matrix degrading enzyme in response to chemokine activation. Int J Oncol 18: 11-16PubMedGoogle Scholar
  27. Romagnani P, Annunziato F, Lasagni L, Lazzeri E, Beltrame C, Francalanci M, Uguccioni M, Galli G, Cosmi L, Maurenzig L, Baggiolini M, Maggi E, Romagnani S and Serio M (2001) Cell cycle-depedent expression of CXC chemokine receptor 3 by endothelial cells mediates angiostatic activity. J Clin Invest 107: 53-63PubMedCrossRefGoogle Scholar
  28. Rozman C, Feliu E, Berga L, Reverter JC, Climent C and Ferran MJ (1989) Age-related variations of fat tissue fraction in normal human bone marrow depend both on size and number of adipocytes: a stereological study. Exp Hematol 17: 34-37PubMedGoogle Scholar
  29. Shigeno Y, Ashton BA (1995) Human bone-cell proliferation in vitro decreases with human donor age. J Bone Joint Surg Br 77: 139-142PubMedGoogle Scholar
  30. Sotsios Y, Whittaker GC, Westwick J and Ward SG (1999) The CXC chemokine stromal cell-derived factor activates a Gi-coupled phosphoinositide 3-kinase in T lymphocytes. J Immunol 163: 5954-5963PubMedGoogle Scholar
  31. Tuner SJ, Domin J, Waterfield MD, Ward SG and Westwick J (1998) The CC chemokine monocyte chemotactic peptide-1 activates both the class 1 p85/p110 phosphatidylinositol-3-kinase and the class II P13K-C2?. J Biol Chem 273: 25987-25995CrossRefGoogle Scholar
  32. Uguccioni M, D'Apuzzo M, Loetscher M, Dewald B and Baggiolini M (1995) Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1 and MIP-1 on human monocytes. Eur J Immunol 25: 64-68PubMedGoogle Scholar
  33. Yudoh K, Matsuno H, Nakazawa F, Katayama R and Kimura T (2001) Reconstituting telomerase activity using the telomerase catalytic subunit prevents the telomere shorting and replicative senescence in human osteoblasts. J Bone Miner Res 16: 1453-1464PubMedCrossRefGoogle Scholar
  34. Zlotnik A and Yoshie O (2001) Chemokines: a new classification system and their role in immunity. Immunity 12: 121-127CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Gina Lisignoli
    • 1
  • Anna Piacentini
    • 1
  • Stefania Toneguzzi
    • 1
  • Francesco Grassi
    • 1
  • Matilde Tschon
    • 1
  • Sandra Cristino
    • 1
  • Andrea Facchini
    • 1
    • 2
  • Erminia Mariani
    • 1
    • 2
  1. 1.Laboratorio di Immunologia e GeneticaIstituti Ortopedici Rizzoli, via diBolognaItaly
  2. 2.Dipartimento di Medicina Interna e GastroenterologiaUniversità degli Studi di BolognaBolognaItaly

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