Skip to main content
SpringerLink
Log in

Time-course of mast cell accumulation in rat bone marrow after ovariectomy

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

We previously reported that mast cells accumulate in the tibia bone marrow of ovariectomized (OVX) rats. In this study, the timing of mast cell accumulation and osteoclast generation were compared to determine whether or not mast cell accumulation preceded osteoclast recruitment after ovariectomy. This may be significant because of the number of cytokines released by mast cells that are potentially active on resorption. Sprague-Dawley rats (120) aged 12 weeks were OVX or sham-operated, and killed on days 4, 7, 14, 28, and 56 postsurgery. Ten additional intact rats were used as baseline controls. Ovariectomy was confirmed by a sharp and sustained fall in serum estradiol. The loss in trabecular bone volume (BV/TV) began on day 7, reaching 80% on day 56 (P<0.001 vs baseline controls). The number of osteoclasts (N.OC/TBPm) increased in the OVX rats between days 4 and 7 (+130%;P<0.001), and continued rising to day 28. During the next month, it decreased greatly (−63%,P<0.001 on day 56 vs day 28). In the sham-treated rats, few mast cells were scattered in the bone marrow (1.9 cells/mm2 in the baseline controls). Their number fluctuated during the experimental period, but at each time-point it was lower than in the OVX rats. They were predominantly (90%) of the mucosal subtype. In the OVX rats, their number doubled between days 4 and 14 (P<0.001), reached 8.6 cells/mm2 on day 28 (a 5.4-fold increase compared with day 4 OVX rats), and plateaued for the next 4 weeks. OVX had no effects on mast cell subtypes. In conclusion, mast cell accumulation and osteoclast differentiation are precocious and concomitant; this does not support a direct role for mast cells in osteoclast recruitment. Rather, the two cell populations may derive from a common precursor or be targeted simultaneously by estrogen depletion through common stimulator(s). Mast cell hyperplasia appears to be a significant, and usually unknown, manifestation of ovariectomy in the bone marrow environment.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Saffar JL, Klapisz-Wolikow M (1990) Changes in mast cell number during the activation phase of an induced synchronized remodeling sequence in the rat. Bone 11:369–372

    Article  PubMed  CAS  Google Scholar 

  2. Dobigny C, Saffar JL (1991) Partial inhibition of bone resorption by disodium cromoglycate in a synchronized model of bone remodeling. Agents Actions 33:326–329

    Article  PubMed  CAS  Google Scholar 

  3. Lesclous Ph, Saffar JL (1999) Mast cells accumulate in rat bone marrow after ovariectomy. Cells Tissues Organs 164:23–29

    Article  PubMed  CAS  Google Scholar 

  4. Ellis HA, Peart KM (1976) Iliac bone marrow mast cells in relation to the renal osteodystrophy of patients treated by haemodialysis. J Clin Pathol 29:502–516

    PubMed  CAS  Google Scholar 

  5. Fallon MD, Whyte MP, Craig RB, Teitelbaum SL (1983) Mast-cell proliferation in postmenopausal osteoporosis. Calcif Tissue Int 35:29–31

    Article  PubMed  CAS  Google Scholar 

  6. McKenna MJ (1994) Histomorphometric study of mast cells in normal bone, osteoporosis, and mastocytosis using a new stain. Calcif Tissue Int 55:257–259

    Article  PubMed  CAS  Google Scholar 

  7. Feik SA, Storey E (1979) Low calcium/high phosphorus rickets in rats. I Mast cell changes. Pathology 11:641–652

    PubMed  CAS  Google Scholar 

  8. Rockoff SD, Amstrong JD (1970) Parathyroid hormone as a stimulus to mast cell accumulation in bone. Calcif Tissue Res 5:49–55

    Article  PubMed  CAS  Google Scholar 

  9. Rasmussen P (1972) An experimental study of mast cells in the rat metaphysis. Calcif Tissue Res 9:325–330

    Article  PubMed  CAS  Google Scholar 

  10. Andrew SM, Freemont AJ (1993) Skeletal mastocytosis. J Clin Pathol 46:1033–1035

    PubMed  CAS  Google Scholar 

  11. Chines A, Pacifici R, Avioli LV, Teitelbaum SL, Korenblat PE (1991) Systemic mastocytosis presenting as osteoporosis—a clinical and histomorphometric study. J Clin Endocrinol Metab 72:140–144

    Article  PubMed  CAS  Google Scholar 

  12. de Gennes C, Kuntz D, de Vernejoul MC (1992) Bone mastocytosis—a report of nine cases with a bone histomorphometric study. Clin Orthop Rel Res 279:281–291

    Google Scholar 

  13. Harvey JA, Anderson HC, Borek D, Morris D, Lukert BP (1989) Osteoporosis associated with mastocytosis confined to bone: report of two cases. Bone 10:237–241

    Article  PubMed  CAS  Google Scholar 

  14. Metcalfe DD, Baram D, Mekori YA (1997) Mast cells. Physiol Rev 77:1033–1079

    PubMed  CAS  Google Scholar 

  15. Theoharides TC (1996) The mast cell: a neuroimmunoendocrine master player. Int J Tissue React 18:1–21

    PubMed  CAS  Google Scholar 

  16. Jilka RL (1998) Cytokines, bone remodeling, and estrogen deficiency: a 1998 update. Bone 23:75–81

    Article  PubMed  CAS  Google Scholar 

  17. Liggett W, Shevde N, Anklesaria P, Sohoni S, Greenberger J, Glowacki J (1993) Effects of macrophage colony-stimulating and granulocyte-macrophage colony-stimulating factor on osteoclastic differentiation of hematopoietic progenitor cells. Stem Cells 11:398–411

    PubMed  CAS  Google Scholar 

  18. Chowdhury MH, Hamada C, Dempster DW (1992) Effects of heparin on osteoclast activity. J Bone Miner Res 7:771–777

    PubMed  CAS  Google Scholar 

  19. Fuller K, Chambers TJ, Gallagher AC (1991) Heparin augments osteoclast resorption-stimulating activity in serum. J Cell Physiol 147:208–214

    Article  PubMed  CAS  Google Scholar 

  20. Ginsberg JS, Kowalchuk G, Hirsh J, Brilledwards P, Burrows R, Coates G, Webber C (1990) Heparin effect on bone density. Thromb Haemost 64:286–289

    PubMed  CAS  Google Scholar 

  21. Muir JM, Hirsh J, Weitz JI, Andrew M, Young E, Shaughnessy SGA (1997) Histomorphometric comparison of the effects of heparin and low-molecular-weight heparin on cancellous bone in rats. Blood 89:3236–3242

    PubMed  CAS  Google Scholar 

  22. Enerbäck L (1986) Mast cell heterogeneity: the evolution of the concept of a specific mucosal mast cell. In: Befus AD, Bienenstock J, Denburg JA (eds) Mast cell differentiation and heterogeneity. Raven Press, New York, pp 1–26

    Google Scholar 

  23. Dimitriadou V, Buzzi MG, Moskowitz MA, Theoharides TC (1991) Trigeminal sensory fiber stimulation induces morphological changes reflecting secretion in rat dura mater mast cells. Neuroscience 44:97–112

    Article  PubMed  CAS  Google Scholar 

  24. Frost HM, Jee WSS (1992) On the rat model of human osteopenias and osteoporosis. Bone Miner 18:227–236

    Article  PubMed  CAS  Google Scholar 

  25. Wronski TJ, Cintron M, Dann LM (1988) Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tissue Int 43:179–183

    PubMed  CAS  Google Scholar 

  26. Jilka RL, Takahashi K, Munshi M, Williams DC, Roberson PK, Manolagas SC (1998) Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow—evidence for autonomy from factors released during bone resorption. J Clin Invest 101:1942–1950

    Article  PubMed  CAS  Google Scholar 

  27. Matayoshi A, Brown C, Dipersio JF, Haug J, Abuamer Y, Liapis H, Kuestner R, Pacifici R (1996) Human blood-mobilized hematopoietic precursors differentiate into osteoclasts in the absence of stromal cells. Proc Natl Acad Sci USA 93:10785–10790

    Article  PubMed  CAS  Google Scholar 

  28. Mbalaviele G, Jaiswal N, Meng A, Cheng LZ, Van den Bos C, Thiede M (1999) Human mesenchymal stem cells promote human osteoclast differentiation from CD34+ bone marrow hematopoietic progenitors. Endocrinology 140:3736–3743

    Article  PubMed  CAS  Google Scholar 

  29. Ishizaka T, Mitsui H, Yanagida M, Miura T, Dvorak AM (1993) Development of human mast cells from their progenitors. Curr Opin Immunol 5:937–943

    Article  PubMed  CAS  Google Scholar 

  30. Demulder A, Suggs SV, Zsebo KM, Scarcez T, Roodman GD (1992) Effects of stem cell factor on osteoclast-like cell formation in long-term human marrow cultures. J Bone Miner Res 7:1337–1344

    PubMed  CAS  Google Scholar 

  31. Muguruma Y, Lee MY (1998) Isolation and characterization of murine clonogenic osteoclast progenitors by cell surface phenotype analysis. Blood 91:1272–1279

    PubMed  CAS  Google Scholar 

  32. van't Hof RJ, von Lindern M, Nijweide PJ, Beug H (1997) Stem cell factor stimulates chicken osteoclast activity in vitro. FASEB J 11:287–293

    Google Scholar 

  33. Aye MT, Hashemi S, Leclair B, Zeibdawi A, Trudel E, Halpenny M, Fuller V, Cheng G (1992) Expression of stem cell factor and c-kit mRNA in cultured endothelial cells, monocytes and cloned human bone marrow stromal cells (CFURF). Exp Hematol 20:523–527

    PubMed  CAS  Google Scholar 

  34. Toksoz D, Zsebo KM, Smith KA, Hu S, Brankow D, Suggs SV, Martin FH, Williams DA (1992) Support of human hematopoiesis in long-term bone marrow cultures by murine stromal cells selectively expressing the membrane-bound and secreted forms of the human homolog of the steel gene product, stem cell factor. Proc Natl Acad Sci USA 89:7350–7354

    PubMed  CAS  Google Scholar 

  35. Blair HC, Dong SS, Julian BA (1999) Expression of stem cell factor by osteoblasts in normal and hyperparathyroid bone: relation to ectopic mast cell differentiation. Virchows Arch 35:50–57

    Article  Google Scholar 

  36. Ahmed N, Khokher MA, Hassan HT (1999) Cytokine-induced expansion of human CD34+ stem/progenitor and CD34+CD41+ early megakariocytic marrow cells cultured on normal osteoblasts. Stem Cells 17:92–99

    Article  PubMed  CAS  Google Scholar 

  37. Vliagoftis H, Dimitriadou V, Boucher W, Rozniecki JJ, Correia I, Raam S, Theoharides TC (1992) Estradiol augments while tamoxifen inhibits rat mast cell secretion. Int Arch Allergy Immunol 98:398–409

    Article  PubMed  CAS  Google Scholar 

  38. Graves L, Stechsculte DJ, Morris DC, Lukert BP (1990) Inhibition of mediator release in systemic mastocytosis is associated with reversal of bone changes. J Bone Miner Res 5:1113–1120

    Article  PubMed  Google Scholar 

  39. Schneider E, Piquet-Pellorce C, Dy M (1990) New role for histamine in interleukin-3-induced proliferation of hematopoietic stem cells. J Cell Physiol 143:337–343

    Article  PubMed  CAS  Google Scholar 

  40. Nakamura M, Kuroda H, Narita K, Endo Y (1996) Parathyroid hormone induces a rapid increase in the number of active osteoclasts by releasing histamine from mast cells. Life Sci 58:1861–1868

    Article  PubMed  CAS  Google Scholar 

  41. Dobigny C, Saffar JL (1997) H1 and H2 histamine receptors modulate osteoclastic resorption by different pathways: evidence obtained by using receptor antagonists in a rat synchronized resorption model. J Cell Physiol 173:10–18

    Article  PubMed  CAS  Google Scholar 

  42. Belanger LF (1977) Variations in the mast cell populations of skin and bone marrow in magnesium-deprived rats. The influence of sex hormones. J Nutr 107:2164–2170

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Biologie et Physiopathologie Crânio-Faciales, Groupe Physiopathologie Osseuse, Faculté de Chirurgie Dentaire, Université René Descartes (Paris-V), 1, rue Maurice Arnoux, 92120, Montrouge, France

    Ph. Lesclous, D. Guez, A. Llorens & J. L. Saffar

Authors
  1. Ph. Lesclous
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Guez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Llorens
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. L. Saffar
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lesclous, P., Guez, D., Llorens, A. et al. Time-course of mast cell accumulation in rat bone marrow after ovariectomy. Calcif Tissue Int 68, 297–303 (2001). https://doi.org/10.1007/BF02390837

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02390837

Key words

Search

Navigation