Journal of Bone and Mineral Metabolism

, Volume 7, Issue 3, pp 38–43 | Cite as

Effect of ascorbic acid deficiency on calcium metabolism in bone of rat with hereditary defect in L-ascorbic acid biosynthesis

  • Toshitsugu Sugimoto
  • Masaaki Fukase
  • Tohru Tsunenari
  • Masaharu Tsutsumi
  • Susumu Makino
  • Yoshiyuki Hayashi
  • Takuo Fujita
Original Articles
  • 36 Downloads

Abstract

A strain of Wistar rat with a hereditary defect in L-ascorbic acid biosynthesis named osteogenesis disorder (OD) rat was used to explore the effect of ascorbic acid deficiency on bone metabolism. OD rats showed lower levels of serum phosphorus, alkaline phosphatase and urinary hydroxyproline than normal rats. Bone histological studies revealed that the essential feature of OD rats was the failure of bone formation. Very few osteoblasts were seen, but mineralization per se seemed to occur normally despite impaired formation of a new matrix. The cAMP response of the bone to parathyroid hormone (PTH) was examined, using isolated perfused femora. Cyclic AMP response to PTH was significantly lower in OD rats than in normal rats.

OD rats showed a histological picture with severely reduced bone formation and impaired cAMP response to PTH, which suggests that ascorbic acid deficiency might induce osteoblastic insufficiency. OD rats provide us a useful animal model to study the effect of ascorbic acid deficiency on bone metabolism.

Key Words

Ascorbic acid-Bone-Osteoblast 

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References

  1. 1.
    Barnes ML. Function of ascorbic acid in collagen metabolism. Ann NY acad Sci. 258,264–277, 1975PubMedGoogle Scholar
  2. 2.
    Bates CJ. Vitamin C deficiency in guinea pigs: variable sensitivity of collagen at different sites. Internat J Vit Nutr Res. 49, 77–86, 1979Google Scholar
  3. 3.
    Chen TL and Raisz LG. The effects of asorbic acid deficiency on calcium and collagen metabolism in cultured fetal rat bones. Calif Tissue Res. 17, 113–127, 1975.Google Scholar
  4. 4.
    Sodek J, Feng J, Yen EHK and Melcher AH. Effects of ascorbic acid on protein synthesis and collagen hydroxylation in continuous flow organ cultures of adult mouse periodontal tissues. Calcif Tissue Int. 34, 408–415, 1982/PubMedGoogle Scholar
  5. 5.
    Chojkier M, Spanheimer R and Peterkofsky B. Specifically decreased collagen biosynthesis in scurvy dissociated from an effects on proline hydroxylation and correlated with body weight loss: In vitro studies in guinea pig calvarial bones. J Clin Invest. 72, 826–835, 1983.PubMedCrossRefGoogle Scholar
  6. 6.
    Sugimoto T, Nakada M, Fukase M, Imai Y, Kinoshita Y and Fujita T. Effects of ascorbic acid on alkaline phosphatase activity and hormone resposiveness in the osteoblastic osteosarcoma cell line UMR-106. Calcif Tissue Int. 39, 171–174, 1986.PubMedGoogle Scholar
  7. 7.
    Mizushima Y, Harauchi T, Yoshizaki T and Makino S. A rat mutant unable to synthesize vitamin C. Experientia. 40, 359–361, 1984.CrossRefPubMedGoogle Scholar
  8. 8.
    Sugimoto T, Fukase M, Tsutsumi M, Imai Y, Hishikawa R, Yoshimoto Y and Fujita T. Additive effects of parathyroid hormone and calcitonin on adenosine 3′, 5′-mono-phosphate release in newly established perfusion system of rat femur. Endocrinology. 117, 1901–1905, 1985.PubMedGoogle Scholar
  9. 9.
    Sugimoto T, Fukase M, Tsutsumi M, Nakada M, Hishikawa R, Tsunenari Y, Yoshimoto Y abd Fujita T. Impaired parathyroid hormone-stimulated adenosine 3′, 5′-monophosphate release by isolated perfused bones obtained from vitamin D-deficient rats. Endocrinology. 118, 1808–1813, 1986.PubMedGoogle Scholar
  10. 10.
    Connerty HV and Briggs AR. Determination of serum calcium by means of ophocresolphtahlein complexone. Am J Clin Path. 45, 290–296, 1966.PubMedGoogle Scholar
  11. 11.
    Lowry OH and Lopez JA. The determination of inorganic phosphate in the presence of labile phosphate esters. J Biol Chem. 162, 421–428, 1946.Google Scholar
  12. 12.
    Hausamen TV, Helger R, Rick W and Gross W. Optimal condition or the determination of serum alkaline phosphatase by a new kinetic method. Clin Chim Acta. 15, 241–245, 1967.CrossRefGoogle Scholar
  13. 13.
    Kivirikko Kl, Laitinen O and Prockop DJ. Modifications of a specific assay for hydroxyproline in urine. Anal Biochem. 19, 249–255, 1967.CrossRefPubMedGoogle Scholar
  14. 14.
    Seelig HP. The Jaffe reaction with creatinine: the reaction product and general reaction conditions. Z Klin Chem Kin Biochem. 7, 581–585, 1969.Google Scholar
  15. 15.
    Steiner Al, Kipnis DM, Utiger R and Parker C. Radioimmunoassay for the measurement of adenosine 3′, 5′-monophosphate. Proc Natl Acad Sci USA. 64, 367–373, 1969.PubMedGoogle Scholar
  16. 16.
    Ramp WK and Thornton PA. Ascorbic acid and the calcium metabolism of embryonic chick tibiae. Proc Soc Exp Biol (NY). 137, 273–276, 1971.Google Scholar
  17. 17.
    Benade L, Howard T and Burk D. Synergistic killing of Ehrlich ascites carcinoma cells by ascorbate and 3-amino-1,2,4-triazole. Oncology (Basal). 23, 33–43, 1969.Google Scholar
  18. 18.
    Josephy PD, Palcic B and Skarsgard LD. Ascorbate-enhanced cytotoxicity of misomidazole. Nature. 271, 370–372, 1978.CrossRefPubMedGoogle Scholar
  19. 19.
    Koch CJ and Biaglow JE. Toxicity, radiation sensitivity modification and metabolic effects of dehydroascorbate and ascorbate in mammalian cells. J Cell Physiol. 94, 299–306, 1978.CrossRefPubMedGoogle Scholar
  20. 20.
    Luben RA, Wong GL and Chon DV. Biochemical characterization with parathyroid hormone and calcitonin of isolated bone cells: Endocrinology. 99, 526–534, 1976.PubMedCrossRefGoogle Scholar
  21. 21.
    Murad S, Grove D, Lindberg KA, Reynolds G, Sivarajah A and Pinnell SR. Regulation of collagen synthesis by ascorbic acid. Proc Natl Acad Sci USA 78, 2879–2882, 1981.PubMedGoogle Scholar
  22. 22.
    Chase LR, Fedack SA and Aurbach GD. Activation of skeletal adenyl cyclase by parathyroid hormone in vitro. Endocrinology. 84, 761–769, 1969.PubMedGoogle Scholar
  23. 23.
    Chase LR and Aurbach GD. The effect of parathyroid hormone on the concentration of adenosine 3′, 5′-monophosphate in skeletal tissue in vitro. J Biol Chem 245, 1520–1526, 1970.PubMedGoogle Scholar
  24. 24.
    Vaes G. Parathyroid hormone-like action of N6-2′-O-dibutyryl adenosine-3′, 5′ (cyclic) — monophosphate on bone explants in tissue culture. Nature. 219, 939–940, 1968.PubMedGoogle Scholar
  25. 25.
    Herrmann-Erlee MPM and Konijin TM. Effect of parathyroid extract on cyclic AMP content of embryonic mouse calvaria. Nature. 227,177–178, 1979.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Bone Metabolism Research 1989

Authors and Affiliations

  • Toshitsugu Sugimoto
    • 1
  • Masaaki Fukase
    • 1
  • Tohru Tsunenari
    • 1
  • Masaharu Tsutsumi
    • 1
  • Susumu Makino
    • 2
  • Yoshiyuki Hayashi
    • 2
  • Takuo Fujita
    • 2
  1. 1.Third Division, Department of MedicineKobe University School of MedicineKobeJapan
  2. 2.Aburabi laboratories, Shionogi Reserch LaboratoriesShionogi & Co.ShigaJapan

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