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Protracted Systemic Changes in Bone Biology after Segmented Unloading in the Rat

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Abstract

To investigate whether the decreased bone formation observed in most experimental situations of disuse was caused by an increased inhibition by the bone microenvironment of osteoblast (OB) proliferation, we studied the inhibiting power on ROS 17/2.8 proliferation of the bone marrow extracellular fluid (IPEF) in loaded and unloaded bones of rats submitted to two situations of partial disuse: tail suspension (TS) for 3 days to 2 weeks and around the knee tenectomy (KT) for 2–10 weeks. Histomorphometric parameters and osteoblast precursors dynamics were studied in parallel. Bone volume was lost in the unloaded bones, but not in loaded bones, in both experimental situations. Bone formation was low at early times (7 - 14 days) in TS rats. However, in KT at later times (4 - 10 weeks), the osteoblastic index of the unloaded tibia was increased. IPEF was not increased in the unloaded bones 3–7 days after TS. It was decreased later in the course of unloading (after 2 weeks of TS and 2–10 weeks after KT). This decrease was observed in the loaded bones as well. Unexpectedly, we also found that the number of FCFUs was decreased in both loaded and unloaded limbs in TS and KT, and that the yield of cells obtained in primary culture from tibial metaphysis was decreased in both tibiae from KT animals. These data show that an increased IPEF does not play a role in the early inhibition of bone formation responsible for the loss of bone after unloading in the TS model. Its later decrease could be permissive for the increased osteoblastic index observed in the KT model. They also show that, contrary to the usual assumptions, bone biology is changed all over the skeleton after partial unloading, even if the changes result in bone loss in the unloaded bones only. Thus, as yet, unidentified systemic factors probably superimpose on the local factors that control bone volume.

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References

  1. D Egrise A Vienne D Martin C Chaboteaux P Bergmann A Schoutens (1999) ArticleTitleAge-related inhibitory activity of rat bone marrow supernatant on osteoblast proliferation. J Bone Miner Res 14 2099–2106 Occurrence Handle1:STN:280:DC%2BD3c%2Fos1Crsw%3D%3D Occurrence Handle10620069

    CAS  PubMed  Google Scholar 

  2. M Machwate E Zerath X Holy M Hott D Modrowski A Malouvier PJ Marie (1993) ArticleTitleSkeletal unloading in rat decreases proliferation of rat bone and bone-marrow derived osteoblastic cells. Am J Physiol 264 E790–E799 Occurrence Handle1:STN:280:ByyB2s%2FgtFM%3D Occurrence Handle8498500

    CAS  PubMed  Google Scholar 

  3. MM Chen WSS Jee HZ Ke BY Lin QN Li XJ Li (1992) ArticleTitleAdaptation of cancellous bone to aging and immobilization in growing rats. Anat Rec 234 317–334 Occurrence Handle1:STN:280:ByyD2s3pvVY%3D Occurrence Handle1443661

    CAS  PubMed  Google Scholar 

  4. JE Zerwekh LA Ruml F Gottschalk CYC Pak (1998) ArticleTitleThe effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. J Bone Miner Res 13 1594–1601 Occurrence Handle1:STN:280:DyaK1cvlsVyluw%3D%3D Occurrence Handle9783548

    CAS  PubMed  Google Scholar 

  5. RK Globus DD Bikle BP Halloran ER Morey-Holton (1986) ArticleTitleSkeletal response to dietary calcium in a rat model simulating weightlessness. J Bone Miner Res 1 191–197 Occurrence Handle1:CAS:528:DyaL28XltFCjs70%3D Occurrence Handle3503537

    CAS  PubMed  Google Scholar 

  6. DD Thompson GA Rodan (1988) ArticleTitleIndomethacin inhibition of tenotomy-induced bone resorption in rats . J Bone Miner Res 3 409–414 Occurrence Handle1:CAS:528:DyaL1cXls1ygsb8%3D Occurrence Handle3223355

    CAS  PubMed  Google Scholar 

  7. M Hinsenkamp A Schoutens M Verhas A Verschaeren (1983) Rat model of tibial unloading and over-loading. . Cepadues (Eds) Space physiology. 291–298

    Google Scholar 

  8. M Machwate E Zerath X Holy P Pastoureau PJ Marie (1994) ArticleTitleInsulin-like growth factor-I increases trabecular bone formation and osteoblastic cell proliferation in unloaded rats. Endocrinology 1134 1031–1038

    Google Scholar 

  9. PJ Kostenuik J Harris BP Halloran RT Turner ER Morey-Holton DD Bikle (1999) ArticleTitleSkeletal unloading causes resistance of osteoprogenitor cells to parathyroid hormone and to insulin-like growth factor-I. J Bone Miner Res 14 21–31 Occurrence Handle1:CAS:528:DyaK1MXlsVWiug%3D%3D

    CAS  Google Scholar 

  10. T Tsuji FJ Hughes CAG McCulloch AH Melcher (1990) ArticleTitleEffects of donor age on osteogenic cells of rat bone marrow in vitro. Mech Aging Dev 51 121–132 Occurrence Handle10.1016/0047-6374(90)90094-V Occurrence Handle1:STN:280:By%2BC2szjvVw%3D Occurrence Handle2308388

    Article  CAS  PubMed  Google Scholar 

  11. D Egrise D Martin A Vienne P Neve A Schoutens (1992) ArticleTitleThe number of fibroblastic colonies formed from bone marrow is decreased and the in vitro proliferation rate of trabecular bone cells increased in aged rats. Bone 13 355–361 Occurrence Handle1:STN:280:ByyD2c%2FntVw%3D Occurrence Handle1419376

    CAS  PubMed  Google Scholar 

  12. R Quarto D Thomas CT Liang (1995) ArticleTitleBone progenitor cell deficits and the age-associated decline in bone repair capacity. Calcif Tissue Int 56 123–129 Occurrence Handle1:CAS:528:DyaK2MXkvVylu7g%3D Occurrence Handle7736320

    CAS  PubMed  Google Scholar 

  13. SA Dodson GW Bernard A Barrie Kenney FA Carranza (1996) ArticleTitleIn vitro comparison of aged and young osteogenic and hemopoietic bone marrow stem cells and their derivative colonies. J Periodontol 67 184–196 Occurrence Handle1:STN:280:BymB28risl0%3D Occurrence Handle8708948

    CAS  PubMed  Google Scholar 

  14. A Scutt U Kollenkirchen P Bertram (1996) ArticleTitleEffect of age and ovariectomy on fibroblastic colony-forming unit numbers in rat bone marrow. Calcif Tissue Int 59 309–310 Occurrence Handle10.1007/s002239900130 Occurrence Handle1:CAS:528:DyaK28XlvFCnu7w%3D Occurrence Handle8781059

    Article  CAS  PubMed  Google Scholar 

  15. C Tabuchi DJ Simmons A Fausto JE Russell I Binderman LV Avioli (1986) ArticleTitleBone deficit in ovariectomized rats. J Clin Invest 78 637–642 Occurrence Handle1:CAS:528:DyaL28XmtF2mtbo%3D Occurrence Handle3528218

    CAS  PubMed  Google Scholar 

  16. Roberts WE, Morey-Holton E, Gonsalves MR (1984) Sensitivity of bone cell populations to weightlessness and simulated weightlessness. Bone Mineralisation Workshop, Brussels (ESA SP-203):67-72

  17. PJ Marie (1995) ArticleTitleHuman endosteal osteoblastic cells: relationship with bone formation. Calcif Tissue Int 56 IssueIDsuppl 1 S13–S16 Occurrence Handle1:CAS:528:DyaK2MXkvVKktbY%3D Occurrence Handle7719974

    CAS  PubMed  Google Scholar 

  18. T Thomas L Vico TM Skerry F Caulin LE Lanyon Ch Alexandre MH Lafage (1996) ArticleTitleArchitectural modifications and cellular response during disuse-related bone loss in calcaneus of the sheep. Am J Physiol 80 IssueID1 198–202 Occurrence Handle1:STN:280:BymH3czgtlc%3D

    CAS  Google Scholar 

  19. P Bergmann A Heilporn A Schoutens J Paternot A Tricot (1977) ArticleTitleLongitudinal study of calcium and bone metabolism in paraplegic patients. Paraplegia 15 IssueID2 147–159 Occurrence Handle1:STN:280:CSeD3M7itFI%3D Occurrence Handle198726

    CAS  PubMed  Google Scholar 

  20. H Drissi A Lomri F Lasmoles X Holy E Zerath PJ Marie (1999) ArticleTitleSkeletal unloading induces biphasic changes in insulin-like growth factor-I mRNA levels and osteoblast activity. Exp Cell Res 251 275–284 Occurrence Handle10.1006/excr.1999.4539 Occurrence Handle1:CAS:528:DyaK1MXlsFyiu7g%3D Occurrence Handle10471313

    Article  CAS  PubMed  Google Scholar 

  21. A Sakai T Nakamura H Tsurukami R Okazaki S Nishida Y Tanaka T Norimura K Suzuki (1996) ArticleTitleBone marrow capacity for bone cells and trabecular bone turnover in immobilized tibia after sciatic neurectomy in mice. Bone 18 479–486 Occurrence Handle1:STN:280:ByiD3MjosFc%3D Occurrence Handle8864470

    CAS  PubMed  Google Scholar 

  22. DJ Simmons L Kidder M Thomas (1990) ArticleTitleEffect of cortisone on cells at the bone-marrow interface. Calcif Tissue Int 46 327–332 Occurrence Handle1:CAS:528:DyaK3cXktFyjsLg%3D Occurrence Handle2110855

    CAS  PubMed  Google Scholar 

  23. P Hernigou F Beaujean JC Lambotte (1999) ArticleTitleDecrease in the mesenchymal stem-cell pool in the proximal femur in corticosteroid-induced osteonecrosis. J Bone Joint Surg 81 IssueID2 349–355 Occurrence Handle10.1302/0301-620X.81B2.8818 Occurrence Handle1:STN:280:DyaK1M3hvFKrtw%3D%3D

    Article  CAS  Google Scholar 

  24. BP Halloran DD Bikle J Harris HC Foskett E Morey-Holton (1993) ArticleTitleSkeletal unloading decreases production of 1,25-dihyroxyvitamin D. Am J Physiol 264 E712–E716 Occurrence Handle1:CAS:528:DyaK3sXkvVOhurs%3D Occurrence Handle8498493

    CAS  PubMed  Google Scholar 

  25. SM Wimalawansa SJ Wimalawansa (1999) ArticleTitleSimulated weghtlessness-induced attenuation of testosterone production may be responsible for bone loss. Endocrine 10 IssueID3 253–260 Occurrence Handle1:CAS:528:DyaK1MXlt1Ols7w%3D Occurrence Handle10484289

    CAS  PubMed  Google Scholar 

  26. E Zérath X Holy SG Roberts C André S Renault M Hott PJ Marie (2000) ArticleTitleSpaceflight inhibits bone formation independent of corticosteroid status in growing rats. J Bone Miner Res 15 1310–1320 Occurrence Handle10893679

    PubMed  Google Scholar 

  27. JE Royland LJ Weber M Fitzpatrick (1994) ArticleTitleTestes size and testosterone levels in a model for weightlessness. Life Sci 54 IssueID8 545–554 Occurrence Handle10.1016/0024-3205(94)90005-1 Occurrence Handle1:CAS:528:DyaK2cXhsFCis7w%3D Occurrence Handle8107532

    Article  CAS  PubMed  Google Scholar 

  28. DR Deaver RP Amann RH Hammerstedt R Ball DN Veeramachaneni XJ Musacchia (1992) ArticleTitleEffects of caudal elevation on testicular function in rats. Separation of effects on spermatogenesis and steroidogenesis. J Androl 13 IssueID3 224–23l Occurrence Handle1:CAS:528:DyaK38XltVCms7s%3D Occurrence Handle1351049

    CAS  PubMed  Google Scholar 

  29. SK Grinspoon HB Baum V Kim C Coggins A Klibanski (1995) ArticleTitleDecreased bone formation and increased mineral dissolution during acute fasting in young women. J Clin Endocrinol Metabl 80 IssueID12 3628–3633 Occurrence Handle1:CAS:528:DyaK2MXpvFSjurk%3D

    CAS  Google Scholar 

  30. SM Talbott MM Rothkopf SA Shapses (1998) ArticleTitleDietary restriction of energy and calcium alters bone turnover and density in younger and older female rats. J Nutrition 128 640–645 Occurrence Handle1:CAS:528:DyaK1cXhs1Wksb4%3D

    CAS  Google Scholar 

  31. PW Nathanielsz (1970) ArticleTitleThe effect of diet and acute starvation on the deiodination of thyroxine and triiodothyronine in the thyroidectomized rat. J Physiol 206 701–710 Occurrence Handle1:CAS:528:DyaE3cXpsl2gsg%3D%3D Occurrence Handle5498513

    CAS  PubMed  Google Scholar 

  32. G Van Den Berghe F De Zegher R Bouillon (1998) ArticleTitleAcute and prolonged critical illness as different neuroendo- crine paradigms. J Clin Endocrinol Metab 83 IssueID6 1827–1834 Occurrence Handle9626104

    PubMed  Google Scholar 

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Acknowledgements

We gratefully acknowledge Catherine André, Xavier Butigieg, Isabelle Drouet, Bernard Hauquier, Dominique Martin, and Sylvie Renault for their excellent technical help. This work was supported partly by a grant from Université Libre de Bruxelles and by the convention N° 3.4575.01 from Fonds de la Recherche Scientifique Médicale Belge (FRSM).

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Authors and Affiliations

  1. Cliniques Universitaires de l’Université Libre de Bruxelles, Belgium

    D. Egrise, M. Hinsenkamp, A. Schoutens & P. Bergmann

  2. Department of Aerospace Physiology, IMASSA-CERMA, Bretigny sur Orge, France

    X. Holy, L. Begot & E. Zerath

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  1. D. Egrise
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  2. X. Holy
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  3. M. Hinsenkamp
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  7. E. Zerath
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Correspondence to D. Egrise.

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Egrise, D., Holy, X., Hinsenkamp, M. et al. Protracted Systemic Changes in Bone Biology after Segmented Unloading in the Rat . Calcif Tissue Int 73, 56–65 (2003). https://doi.org/10.1007/s00223-002-2085-3

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  • DOI: https://doi.org/10.1007/s00223-002-2085-3

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