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Interleukin-4 as a bone regulatory factor: Effects on murine osteoblast-like cells

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Abstract

Bone remodelling is regulated at the local level by an incompletely elucidated cytokine network. In the present study we have determined the effect of interleukin-4 (IL-4), a cytokine produced by T Iymphocytes and other cells, on the activity of murine osteoblasts. IL-4 (0.1–10 ng/ml) did not influence the proliferation rate of the osteoblast-like cell line MC3T3, but inhibited the expression of alkaline phosphatase. In long-term cultures supplemented with ascorbic acid and glycerophosphate such an effect was accompanied by a retardation of matrix mineralization. IL-4 also stimulated M-CSF expression by MC3T3 cells, both at the RNA and bioactivity levels. However, no stimulation of IL-1, IL-6, GM-CSF or PGE2 production was observed. An IL-4-induced inhibition of alkaline phosphatase expression and retardation of mineralization was also found in cultures of primary osteoblast-like cells isolated from neonatal mice calvariae. These results suggest that IL-4, probably released by cells within the bone marrow, may locally influence the activity of bone-forming cells.

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References

  1. Paul W.E. Interleukin-4: a prototypic immunoregulatory lymphokine. Blood 77: 1859, 1991.

    PubMed  CAS  Google Scholar 

  2. Lewis D.B., Liggit D., Effmann E.L., Motley S.T., Teitelbaum S., Jepsen K.J., Goldstein S.A., Bonadio J., Carpenter J., Perlmutter R.M. Osteoporosis induced in mice by overproduction of interleukin 4. Proc. Natl. Acad. Sci. USA 90: 1168, 1993.

    Article  Google Scholar 

  3. Sudo H., Kodama H., Amagai Y., Yamamoto S., Kasai S. In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J. Cell. Biol. 96: 191, 1983.

    Article  PubMed  CAS  Google Scholar 

  4. Quarles L.D., Yohay D.A., Lever L.W., Caton R., Wenstrup R.J. Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development. J. Bone Miner. Res. 7: 683, 1992.

    Article  PubMed  CAS  Google Scholar 

  5. Jilka R.L. Parathyroid hormone-stimulated development of os-teoclasts in cultures of cells from neonatal murine calvaria. Bone 7: 29, 1986.

    Article  PubMed  CAS  Google Scholar 

  6. Majeska R.J., Nair B.C., Rodan G.A. Glucocorticoid regulation of alkaline phosphatase in the osteoblastic osteosarcoma cell line ROS 17/2.8. Endocrinology 116: 170, 1985.

    Article  PubMed  CAS  Google Scholar 

  7. van de Loosdrecht A.A., Nennie E., Ossenkoppele G.J., Beelen R.H.J., Langenhuijsen M.M.A.C. Cell mediated cytotoxicity against U 937 cells by human monocytes and macrophages in a modified colorimetric assay. A methodological study. J. Immunol. Methods 141: 15, 1991.

    Article  PubMed  Google Scholar 

  8. Rickard D., Russell G., Gowen M. Oestradiol inhibits the release of tumour necrosis factor but not interleukin 6 from adult human osteoblasts in vitro. Osteoporosis Int. 2: 94, 1992.

    Article  CAS  Google Scholar 

  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162: 156, 1987.

    Article  PubMed  CAS  Google Scholar 

  10. Mohan S., Baylink D.J. Bone growth factors. Clin. Orthop. Rel. Res. 263: 30, 1991.

    Google Scholar 

  11. Gowen M. Cytokines and bone metabolism. CRC Press, Boca Raton, 1992.

    Google Scholar 

  12. Bellows CG., Aubin J.E., Heersche J.N.M. Initiation and progression of mineralization of bone nodules formed in vitro: the role of alkaline phosphatase and organic phosphate. Bone Miner 14: 27, 1991.

    Article  PubMed  CAS  Google Scholar 

  13. Mundy G.R. Local factors in bone remodeling. Recent Prog. Horm. Res. 45: 507, 1989.

    PubMed  CAS  Google Scholar 

  14. Shioi A., Teitelbaum S.L., Ross F.P., Welgus H.G., Suzuki H., Ohara J., Lacey D.L. Interleukin-4 inhibits murine osteoclast formation in vitro. J. Cell. Biochem. 47: 272, 1991.

    Article  PubMed  CAS  Google Scholar 

  15. Riancho J.A., Zarrabeitia M.T., Mundy G.R., Yoneda T., González-Macías J. Effects of interleukin-4 on the formation of macrophages and osteoclast-like cells. J. Bone Miner. Res. 8: 1337, 1993.

    Article  PubMed  CAS  Google Scholar 

  16. Riancho JA, Zarrabeitia M.T., Olmos J.M., Amado J.A., González-Marcías J. Effects of interleukin-4 on human osteoblast-like cells. Bone Miner. 21: 53, 1993.

    Article  PubMed  CAS  Google Scholar 

  17. Ueno K., Katayama T., Miyamoto T., Koshihara Y. Interleukin-4 enhances in vitro mineralization in human osteoblast-like cells. Biochem. Biophys. Res. Commun. 189: 1521, 1992.

    Article  PubMed  CAS  Google Scholar 

  18. Phillips W.A., Croatto M., Hamilton J.A. The effect of interleukin-4 on the macrophage respiratory burst is species dependent. Biochem. Biophys. Res. Commun. 82: 727, 1992.

    Article  Google Scholar 

  19. Ohta S., Yamamuro T., Lee K., Okumura H., Kasai R., Hiraki Y., Ikeda T., Iwasaki R., Kikuchi H., Konishi J., Shigeno C. Fracture healing induces the expression of the proto-oncogen c-fos in vivo. Possible involvement of the Fos protein in osteoblast differentiation. FEBS Lett. 284: 42, 1991.

    Article  PubMed  CAS  Google Scholar 

  20. Dokter W.H.A., Esselink M.T., Halie M.R., Vellenga E. Interleukin-4 inhibits the Iipopolysaccharide-induced expression of c-jun and c-fos messenger RNA and activator protein-1 binding activity in human monocytes. Blood 81: 337, 1993.

    PubMed  CAS  Google Scholar 

  21. Hattersley G., Chambers T.J. Effect of interleukin 3 and of granulocyte-macrophage and macrophage colony stimulating factors on osteoclast differentiation from mouse hemopoietic tissue. J. Cell. Physiol. 142: 201, 1990.

    Article  PubMed  CAS  Google Scholar 

  22. Tanaka S., Takahashi N., Udagawa N., Tamura T., Akatsu T., Stanley E.R., Kurokawa T., Suda T. Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast precursors. J. Clin. Invest. 91: 257, 1993.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Supported by a grant from the DGICYT (PM 92/0079).

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Riancho, J.A., González-Marcías, J., Amado, J.A. et al. Interleukin-4 as a bone regulatory factor: Effects on murine osteoblast-like cells. J Endocrinol Invest 18, 174–179 (1995). https://doi.org/10.1007/BF03347799

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