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Bone Resorption Is Inhibited by an Osteocyte-Derived Protein

  • Akiko Ikeda
  • Mari Aoki
  • Katsuki Tsuritani
  • Kayo Kamioka
  • Kenji Hiura
  • Toshio Miyoshi
  • Hiroshi Hara
  • Masayoshi Kumegawa
Conference paper

Summary

In the process of bone resorption, osteoclasts encounter a large number of osteocytes excavated from the bone tissue. For instance, osteocytes released from the collagen matrix have been shown to be engulfed into osteoclasts by phagocytosis. After the osteoclast-osteocyte encounter or incorporation of osteocytes into osteoclasts, it is possible that osteocytes transmit some signals to osteoclasts.

To investigate roles of osteocytes in bone resorption, we examined the homogenate and conditioned medium from purified chick calvarial osteocytes in a pit-formation assay. The osteocyte homogenate markedly inhibited pit formation by unfractionated bone cells, whereas the conditioned medium of the cells had no effect. A novel bone-resorption-inhibitory protein was purified from collagenase-digested chick calvarial fragments enriched in osteocytes. The inhibitory protein, of molecular mass 18.5 kDa, showed significant inhibition of pit formation by purified osteoclasts as well as by unfractionated bone cells. Microinjection of the protein into osteoclasts caused disruption of podosomes in the cells. Thus osteocytes may be involved in the regulation of bone resorption by osteoclasts.

Key words

Osteocyte Osteoclast Bone resorption Pit formation 

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References

  1. 1.
    Parfitt AM (1977) The cellular basis of bone turnover and bone loss. Clin Orthop Relat Res 127:236–247PubMedGoogle Scholar
  2. 2.
    Palumbo C, Palazzini S, Zaff D, Marotti G (1990) Osteocyte differentiation in the tibia of newborn rabbit: an ultrastructural study of the formation of cytoplasmic processes. Acta Anat 137:350–358PubMedCrossRefGoogle Scholar
  3. 3.
    Aarden EM, Buerger EH, Nijweide PJ (1994) Function of osteocytes in bone. J Cell Biochem 55:287–299PubMedCrossRefGoogle Scholar
  4. 4.
    Jones SJ, Gray C, Sakamaki H, Arora M, Boyde A, Gourdie R, Green C (1993) The incidence and size of gap junctions between the bone cells in rat calvaria. Anat Embryol 187:343–352PubMedCrossRefGoogle Scholar
  5. 5.
    Nefussi JR, Sautier JM, Nicolas V, Forest N (1991) How osteoblasts become osteocytes: a decreasing matrix forming process. J Biol Buccale 19:75–82PubMedGoogle Scholar
  6. 6.
    Palumbo C, Palazzani S, Marotti G (1990) Morphological study of intercellular junctions during osteocyte differentiation. Bone 11:401–406PubMedCrossRefGoogle Scholar
  7. 7.
    Marotti G, Ferretti M, Muglia MA, Palumbo C, Palazzini S (1992) A quantitative evaluation of osteoblast-osteocyte relationships on growing endosteal surface of rabbit tibiae. Bone 13:363–368PubMedCrossRefGoogle Scholar
  8. 8.
    Lean JM, Jagger CJ, Chambers TJ, Chow JWM (1994) Increased insulin-like growth factor-1 mRNA expression in osteocytes precedes the increase in bone formation in response to mechanical stimulation. J Bone Miner Res 9 (Suppl 1):S142Google Scholar
  9. 9.
    Price JS, Suswillo RFL, Houston B, Zaman G, Nijweide PJ, Lanyon LE (1995) The expression of bone morphogenetic proteins 6 and 7 in osteocytes: The effects of mechanical strain. J Bone Miner Res 10 (Suppl 1):S307Google Scholar
  10. 10.
    Mikuni-Takagaki Y, Suzuki Y, Kawase T, Saito S (1996) Distinct responses of different populations of bone cells to mechanical stress. Endocrinology 137(5):2028–2035PubMedCrossRefGoogle Scholar
  11. 11.
    Lozupone E, Palumbo C, Favia A, Ferretti M, Palazzini S, Cantatore FP (1996) Intermittent compressive load stimulates osteogenesis and improves osteocyte viability in bones cultured “in vitro”. Clin Rheumatol 15(6):563–572PubMedCrossRefGoogle Scholar
  12. 12.
    Mullender MG, Huiskes R (1997) Osteocytes and bone lining cells: which are the best candidates for mechano-sensors in cancellous bone? Bone 20(6):527–532PubMedCrossRefGoogle Scholar
  13. 13.
    Bonucci E (1981) New knowledge on the origin, function and fate of osteoclasts. Clin Orthop Relat Res 158:252–269PubMedGoogle Scholar
  14. 14.
    Kameda T, Mano H, Yuasa T, Mori Y, Miyazawa K, Shiokawa M, Nakamaru Y, Hiroi E, Hiura K, Kameda A, Yang NN, Hakeda Y, Kumegawa M (1997) Estrogen inhibits bone resorption by directly inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med 186(4):489–495PubMedCrossRefGoogle Scholar
  15. 15.
    Dempster DW, Moonga BS, Stein LS, Horbert WR, Antakly T (1997) Glucocorticoids inhibit bone resorption by isolated rat osteoclasts by enhancing apoptosis. J Endocrinol 154(3):397–406PubMedCrossRefGoogle Scholar
  16. 16.
    Marks SC (1983) The origin of osteoclasts. J Pathol 12:226–256Google Scholar
  17. 17.
    Takahashi T, So S, Wang D, Takahashi K, Kurihara N, Kumegawa M (1986) Phagocytosis of different matrix components by different cell types at bone-forming sites in cultured mouse calvariae. Cell Tissue Res 245:9–17PubMedCrossRefGoogle Scholar
  18. 18.
    Tonna EA (1972) An electron microscopic study of osteocyte release during osteoclasis in mice of different ages. Clin Orthop Relat Res 87:311–317PubMedCrossRefGoogle Scholar
  19. 19.
    Elmardi AS, Katchburian MV, Katchburian E (1990) Electron microscopy of developing calvaria reveals images that suggest that osteoclasts engulf and destroy osteocytes during bone resorption. Calcif Tissue Int 46:239–245PubMedCrossRefGoogle Scholar
  20. 20.
    Maejima-Ikeda A, Aoki M, Tsuritani K, Kamioka K, Hiura K, Miyoshi T, Hara H, Takano-Yamamoto T, Kumegawa M (1997) Chick osteocyte-derived protein inhibits osteoclastic bone resorption. Biochem J 322:245–250PubMedGoogle Scholar
  21. 21.
    Zhang D, Murakami H, Udagawa N, Nakamura I, Saito S, Shibasaki Y, Mori N, Narumiya S, Takahashi N, Suda T (1994) The small GTP-binding protein Rho is involved in osteoclastic bone resorption by regulating podosome formation. J Bone Miner Res 9 (Suppl 1):S131Google Scholar
  22. 22.
    Miura Y, Kikuchi A, Musha T, Kuroda S, Yaku H, Sasaki T, Takai Y (1993) Regulation of morphology by rho p21, its inhibitory GDP/GTP exchange protein (rho GDI) in Swiss 3T3 cells. J Biol Chem 268:510–515PubMedGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1999

Authors and Affiliations

  • Akiko Ikeda
    • 1
  • Mari Aoki
    • 1
  • Katsuki Tsuritani
    • 1
  • Kayo Kamioka
    • 2
  • Kenji Hiura
    • 3
  • Toshio Miyoshi
    • 1
  • Hiroshi Hara
    • 1
  • Masayoshi Kumegawa
    • 2
  1. 1.Medicinal Research LaboratoriesTaisho Pharmaceutical Co., Ltd.Ohmiya, SaitamaJapan
  2. 2.Department of Oral AnatomyMeikai University School of DentistrySakado, SaitamaJapan
  3. 3.Department of Orthodontics, School of DentistryThe University of TokushimaTokushima, TokushimaJapan

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