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Effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on rat bone: Inhibition of bone formation at the endosteal surface of vertebra and tibia

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Abstract

The effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on bone was evaluated by histomorphometry using Sprague-Dawley rats. rh G-CSF was injected at doses of 0, 50, 150, and 450 μg/kg for 6 weeks.In vivo double fluorochrome labeling was performed before sacrifice. No significant change in body weight was observed. Bone mineral density (BMD) of lumbar vertebrae and femora was significantly decreased in G-CSF-treated groups. In the lumbar vertebra, osteoid surface, osteoid thickness, trabecular thickness, and labeled surface in G-CSF-treated groups were also significantly lower. In addition, osteoclast number and osteoclast surface were significantly higher in the G-CSF-treated groups. The endocortical surface at the mid-tibia showed lower labeled surface and mineral apposition rate in G-CSF-treated groups, without significant changes at the periosteal surface. Furthermore, numerous granulocytes fully occupied the bone marrow area. We conclude that proliferating granulocytes in the bone marrow may inhibit bone-forming cells from contacting the bone surface, resulting in reduction of bone formation;and increased osteoclastic bone resorption induced by G-CSF treatment contributed to the reduction of BMD.

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References

  1. Kawahara J, Yanagida M, Kubo K, Ishii H, Amada H, Ishii T, Amano K, Tokiwa T (1990) Toxicological studies on recombinant human granulocyte colony-stimulating factor (rh G-CSF: KRN 8601) (2). Iyakuhin Kenkyu (in Japanese) 22:270–286

    Google Scholar 

  2. Neda, K, Kimura S, Watanabe S, Hosokawa T, Izumi H, Amano K, Tokiwa T (1990) Toxicological studies on recombinant human granulocyte colony-stimulating factor (rh G-CSF: KRN 8601) (3). Iyakuhin Kenkyu (in Japanese) 22:287–306

    Google Scholar 

  3. Baron R, Tross R, Vignery A (1984) Evidence of sequential remodeling in rat trabecular bone: morphology, dynamic histomorphometry, and changes during skeletal maturation. Anat Rec 208:137–145

    Article  PubMed  CAS  Google Scholar 

  4. Frost HM (1969) Tetracycline-based histological analysis of bone remodeling. Calcif Tissue Res 3:211–239

    Article  PubMed  CAS  Google Scholar 

  5. Parfitt AM, Drezner MK, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM, Recker RR (1987) Bone histomorphometry: standardization of nomenclature, symbols, and units. J Bone Miner Res 6:595–610

    Google Scholar 

  6. Recker RR (1983) Bone histomorphometry: techniques and interpretation. CRC Press, Boca Raton, FL, pp 109–142

    Google Scholar 

  7. Recker RR (1983) Bone histomorphometry: techniques and interpretation. CRC Press, Boca Raton, FL, pp 143–224

    Google Scholar 

  8. Shinar DM, Sato M, Rodan GA (1990) The effect of hemopoietic growth factors on the generation of osteoclast-like cells in mouse bone marrow culture. Endocrinology 126: 1728–1735

    Article  PubMed  CAS  Google Scholar 

  9. Hosoi T, Ohuchi S, Orimo H, Mori M (1991) The effect of G-CSF on osteoblast-like cells. Int J Hematol (in Japanese) 54:218

    Google Scholar 

  10. Rosol TJ, Stromberg PC (1990) Effects of large granulocyte leukemia on bone in F344 rats. Vet Phaso 27:391–396

    CAS  Google Scholar 

  11. Whetton AD, Dexter TM (1989) Myeloid haemopoietic growth factors. Biochem Biophys Acta 989:111–132

    PubMed  CAS  Google Scholar 

  12. Ikebuchi K, Clark SC, Ihle JN, Souza LM, Ogawa M (1988) Granulocyte colony-stimulating factor enhances interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 85:3445–3449

    Article  PubMed  CAS  Google Scholar 

  13. Takahashi N, Udagawa N, Akatsu T, Tanaka H, Shionome M, Suda T (1991) Role of colony-stimulating factors in osteoclast development. J Bone Miner Res 6:977–985

    Article  PubMed  CAS  Google Scholar 

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Soshi, S., Takahashi, H.E., Tanizawa, T. et al. Effect of recombinant human granulocyte colony-stimulating factor (rh G-CSF) on rat bone: Inhibition of bone formation at the endosteal surface of vertebra and tibia. Calcif Tissue Int 58, 337–340 (1996). https://doi.org/10.1007/BF02509382

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  • DOI: https://doi.org/10.1007/BF02509382

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