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Inhibitory and stimulatory effects of prostaglandins on osteoclast differentiation

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Abstract

The effect of prostaglandins (PGs) on osteoclast differentiation, an important point of control for bone resorption, is poorly understood. After an initial differentiation phase that lasts at least 4 days, murine monocytes, cocultured with UMR106 osteoblastic cells (in the presence of 1,25-dihydroxyvitamin D3) give rise to tartrate-resistant acid phosphatase (TRAP) positive osteoclast-like cells that are capable of lacunar bone resorption. PGE2 strongly inhibits TRAP expression and bone resorption in these cocultures. To examine further the cellular mechanisms associated with this inhibitory effect, we added PGE2 to monocyte/UMR106 cocultures at specific times before, during, and after this initial 4-day differentiation period. To determine whether this PGE2 inhibition was dependent on the type of stromal cell supporting osteoclast differentiation, we also added PGE2 to cocultures of monocytes with ST2 preadipocytic cells.

Inhibition of bone resorption was greatly reduced when the addition of PGE2 to monocyte/UMR106 cocultures was delayed until the fourth day of incubation; when delayed until the seventh day, inhibition did not occur. PGE2 inhibition of bone resorption was concentration-dependent and at 10−6 M was also mediated by PGE1 and PGF2α. In contrast to its effects on monocyte/UMR106 cocultures, PGE2 stimulated bone resorption in monocyte/ST2 cocultures. Both ST2 cells and UMR106 cells were shown to express functional receptors for PGE2.

These results show that PGs strongly influence the differentiation of osteoclast precursors and that this effect is dependent not only on the type and dose of PG administered, but also on the nature of the bone-derived stromal cell supporting this process.

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References

  1. Lerner UH, Ransjo M, Ljunngren O (1987) Prostaglandin E2 causes transient inhibition of matrix mobilization, matrix degradation, and lysosomal enzyme release from mouse calvarial bones in vitro. Calcif Tissue Res 40: 323–331

    Article  CAS  Google Scholar 

  2. Klein DC, Raisz LG (1970) Prostaglandins: stimulation of bone resorption in tissue cultures. Endocrinology 86: 1436–1440

    PubMed  CAS  Google Scholar 

  3. Schelling SH, Wolfe HJ, Tashjian AH (1980) Role of the osteoclast in prostaglandin E2 simulated bone resorption. Lab Invest 42: 290–295

    PubMed  CAS  Google Scholar 

  4. Santora MG, Jaffe BM, Simmons DJ (1977) Bone resorption in vitro and in vivo in PGE treated mice. Proc Soc Exp Biol Med 156: 373–377

    Google Scholar 

  5. Desimone DP, Greene VS, Hannon KS, Turner RT, Bell NH (1993) Prostaglandin E2 administered by subcutaneous pellets causes local inflammation and systemic bone loss: a model for inflammation-induced bone disease. J Bone Miner Res 8: 625–634

    PubMed  CAS  Google Scholar 

  6. Chambers TJ, McSheehy PMJ, Thompson BM, Fuller K (1985) The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinology 116: 234–239

    PubMed  CAS  Google Scholar 

  7. Fuller K, Chambers TJ (1989) The effect of arachidonic acid metabolites on bone resorption by isolated rat osteoclasts. J Bone Miner Res 4: 209–215

    PubMed  CAS  Google Scholar 

  8. Okuda A, Taylor LM, Heersche JN (1989) Prostaglandin E2 initially inhibits then stimulates bone resorption in isolated rabbit osteoclast cultures. Bone Miner 7: 255–266

    Article  PubMed  CAS  Google Scholar 

  9. Tatevossian A (1973) Effect of parathyroid extract on blood calcium and osteoclast count in mice. Calcif Tissue Res 11: 251–257

    Article  PubMed  CAS  Google Scholar 

  10. Marie PJ, Travers R (1983) Continuous infusion of 1,25-dihydroxyvitamin D3 stimulates bone turnover in the normal young mouse. Calcif Tiss Int 35: 418–425

    Article  CAS  Google Scholar 

  11. Feldman RS, Kreiger NS, Tashjian AH (1980) Effects of parathyroid hormone and calcitonin on on osteoclast formation in vitro. Endocrinology 107: 1137–1143

    PubMed  CAS  Google Scholar 

  12. Collins DA, Chambers TJ (1992) Prostaglandin E2 promotes osteoclast formation in murine hematopoietic cultures through an action on hematopoietic cells. J Bone Miner Res 7: 555–561

    PubMed  CAS  Google Scholar 

  13. Kanatani M, Sugimoto T, Fukase M, Chihara K (1994) The role of interleukin-6 and prostaglandins in the effect of monocyte-conditioned medium on osteoclast formation. Am J Physiol 267: E868–870

    PubMed  CAS  Google Scholar 

  14. Holt I, Davie MW, Braidman IP, Marshal MJ (1994) Interleukin-6 does not mediate the stimulation by prostaglandin E2, parathyroid hormone or 1,25 dihydroxyvitamin D of osteoclast differentiation in neonatal mouse parietal bones. Calcified Tis Res 55: 114–119

    Article  CAS  Google Scholar 

  15. Chenu C, Kurihara N, Mundy GR, Roodman GD (1990) Prostaglandin E2 inhibits formation of osteoclast-like cells in longterm human marrow cultures but is not a mediator of the inhibitory effects of transforming growth factor β. J Bone Miner Res 5: 677–681

    Article  PubMed  CAS  Google Scholar 

  16. Quinn JMW, McGee JO’D, Athanasou NA (1994) Cellular and hormonal factors influencing monocyte differentiation in osteoclastic bone-resorbing cells. Endocrinology 134: 2416–2423

    Article  PubMed  CAS  Google Scholar 

  17. Udagawa N, Takahashi N, Akatsu T, Tanaka H, Sasaki T, Nishihari T, Martin TJ, Suda T (1990) Origin of osteoclasts: mature monocytes and macrophages are capable of differentiation into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci USA 87: 7260–7264

    Article  PubMed  CAS  Google Scholar 

  18. Quinn J, Joyner C, Triffitt JT, Athanasou NA (1992) Polymethyl methacrylate-induced inflammatory macrophages resorb bone. J Bone Joint Surg 74B: 652–658

    Google Scholar 

  19. Takahashi N, Udagawa N, Tanaka S, Murakami H, Owan I, Tamura T, Suda T (1994) Postmitotic osteoclast precursors are mononuclear cells which express macrophage-associated phenotypes. Dev Biol 163: 212–221

    Article  PubMed  CAS  Google Scholar 

  20. Tanaka S, Takahashi N, Udagawa N, Tamura T, Akatsu T, Stanley ER, Kurokawa T, Suda T (1993) Macrophage colony stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. J Clin Invest 91: 257–263

    Article  PubMed  CAS  Google Scholar 

  21. Athanasou NA, Wells CA, Quinn J, Ferguson DP, Heryet A, McGee JO’D (1989) The origin and nature of stromal osteoclast-like multinucleated giant cells in breast carcinoma: implications for tumour osteolysis and macrophage biology. Br J Cancer 59: 491–498

    PubMed  CAS  Google Scholar 

  22. Austyn JM, Gordon S (1981) F4/80, a monoclonal antibody directed specifically against the mouse macrophage. Eur J Immunol 11: 805–815

    Article  PubMed  CAS  Google Scholar 

  23. Gatter KC, Falini B, Mason DY (1984) The use of monoclonal antibodies in histological diagnosis. In: Anthony PP, Mac-Sween RNM (eds) Recent advances in histopathology, no 12. Churchill Livingstone, Edinburgh pp 35–67

    Google Scholar 

  24. Chambers TJ, Ali NN (1983) Inhibition of osteoclastic motility by prostaglandins I1, E1, E2, and 6-oxo-E1. J Pathol 139: 383–397

    Article  PubMed  CAS  Google Scholar 

  25. Tashjian AH, Voelkel EF, Lazzaro M, Goad M, Bosma, Levine L (1987) Tumor necrosis factor-α (cachectin) stimulates bone resorption in mouse calvaria via a prostaglandinmediated mechanism. Endocrinology 120: 2029–2036

    Article  PubMed  CAS  Google Scholar 

  26. Akatsu T, Takahashi N, Debari K, Morita I, Murota S, Nagata N, Takatani O, Suda T (1989) Prostaglandins promote osteoclastlike cell formation by a mechanism involving cyclic adenosine 3′, 5′ monophosphate in mouse bone marrow cultures. J Bone Miner Res 4: 29–35

    Article  PubMed  CAS  Google Scholar 

  27. Partridge NC, Alcorn D, Michelangeli VP, Ryan G, Martin TJ (1983) Morphologic and biochemical characterization of four clonal osteogenic sarcoma cell lines of rat origin. Cancer Res 43: 4308–4314

    PubMed  CAS  Google Scholar 

  28. Coleman RA, Smith WL, Narumiya S (1994) International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. Pharmacol Rev 46: 205–229

    PubMed  CAS  Google Scholar 

  29. Fang MA, Kujubu DA, Hahn TJ (1992) The effects of prostaglandin E2, parathyroid hormone, and epidermal growth factor on mitogenesis, signaling, and primary response genes in UMR 106-01 osteoblast-like cells. Endocrinology 131: 2113–2119

    Article  PubMed  CAS  Google Scholar 

  30. Yamaguchi DT, Green J, Merritt BS, Kleeman CR, Muallem S (1989) Modulation of osteoblast function by prostaglandins. Am J Physiol 257: F755-F61

    PubMed  CAS  Google Scholar 

  31. Sato T, Abe E, Jin CH, Hong MH, Katagiri T, Kinoshita T, Amizuka N, Ozawa N, Suda T (1993) The biological roles of the third component of complement in osteoclast formations. Endocrinology 133: 397–404

    Article  PubMed  CAS  Google Scholar 

  32. Mangham DC, Scoones DJ, Drayson MT (1993) Complement and the recruitment of mononuclear osteoclasts. J Clin Pathol 46: 517–521

    Article  PubMed  CAS  Google Scholar 

  33. Hume DA, Loutit JF, Gordon S (1984) The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of the antigen F4/80 macrophages of bone and associated connective tissue. J Cell Sci 66: 189–194

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Nuffield Department of Pathology, University of Oxford, John Radcliffe Hospital, Headington, 0X3 9DU, Oxford, UK

    J. M. W. Quinn, J. O. D. McGee & N. A. Athanasou

  2. Nuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre, Headington, 0X3 7LD, Oxford, UK

    A. Sabokbar & N. A. Athanasou

  3. INSERM Unit 349, Centre Viggo Petersen, Hôpital Lariboisiére, 75010, Paris, France

    M. Denne & M. -C. de Vernejoul

Authors
  1. J. M. W. Quinn
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  2. A. Sabokbar
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  3. M. Denne
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  4. M. -C. de Vernejoul
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  5. J. O. D. McGee
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  6. N. A. Athanasou
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Quinn, J.M.W., Sabokbar, A., Denne, M. et al. Inhibitory and stimulatory effects of prostaglandins on osteoclast differentiation. Calcif Tissue Int 60, 63–70 (1997). https://doi.org/10.1007/s002239900187

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  • DOI: https://doi.org/10.1007/s002239900187

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