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Surgically induced uremia in rats II: Osseous PTH-susceptible signaling systems as predictors of bone resorption

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Abstract

Predicting the course of parathormone (PTH)-elicited bone turnover in both humans and experimental rat models with moderate chronic uremia, using only standard clinical chemistry analyses, is often difficult. Consequently, rat bone from 1+2/3 nephrectomized animals, after 230 days of progressive renal failure, was examined for PTH-stimulated adenylate cyclase (AC) and phospholipase C (PLC) activities. Correlations to biological parameters related to the function of bone and kidney were made. Reduced renal function was demonstrated by increased serum creatinine; circulating 1,25 dihydroxyvitamin D3 below detection level; diminished renal PTH-elicited AC activity; and decreased urinary cAMP excretion. PTH-activated renal PL-C was also reduced. However, no significant differences were seen in urine creatinine, calcium, phosphate, and hydroxyproline, nor in serum PTH, alkaline phosphatase, calcium, and phosphate. Notwithstanding, renal osteodystrophy developed as estimated by increased plasticity of the long bones, as well as reduction of the diaphyseal (Dd) and inner femoral midshaft (Di) diameters. Femoral cancellous bone exhibited a substantial elevation of both eroded surface (ES) and osteoid surface (OS) as well as a marked reduction in trabecular bone volume (TBV). Calvarial PTH-activated AC was enhanced, whereas corresponding PL-C was markedly reduced. PTH-enhanced AC correlated positively with ES and negatively with Di, respectively. PTH-enhanced PL-C, however, correlated positively with bone calcium content and negatively with ES. Our results indicate that bone modeling and remodeling are to a large extent related to PTH-elicited signaling systems, and cannot easily be predicted by standard clinical chemistry analyses.

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References

  1. Coburn JW, Henry DA (1984) Renal osteodystrophy. Adv Intern Med 30:387–424

    Google Scholar 

  2. Cushner HM, Adams ND (1986) Review: renal osteodystrophy—pathogenesis and treatment. Am J Med Sci 291:264–275

    Google Scholar 

  3. Mankin HJ (1990) Rickets, osteomalacia, and renal osteodystrophy—an update. Orthop Clin North Am 21(1):81–96

    Google Scholar 

  4. Potts JT Jr, Kronenberg HM, Rosenblatt M (1982) Parathyroid hormone: chemistry, biosynthesis, and mode of action. Adv Prot Chem 35:296–323

    Google Scholar 

  5. Klein KL, Maxwell MH (1984) Renal osteodystrophy. Orthop Clin North Am 15(4):687–695

    Google Scholar 

  6. Coburn JW, Slatopolsky E (1981) Vitamin D, parathyroid hormone, and renal osteodystrophy. In: Brenner B, Rector F (eds) The kidney. WB Saunders, Philadelphia, pp 2213–2205

    Google Scholar 

  7. Jablonski G, Klem KH, Attramadal A, Dahl E, Rønningen H, Gautvik KM, et al. (1993) Surgically induced uremia in rats I: effect on bone strength and metabolism. Biosci Rep 13(5):275–287

    Google Scholar 

  8. Jüppner H, Abou-Samra A-B, Freeman M, Kong XF, Schipani E, Richards J, et al. (1991) A G-protein-linked receptor for parathyroid hormone and parathyroid hormone-related peptide. Science 254:1024–1026

    Google Scholar 

  9. Abou-Samra AB, Jüppner H, Force T, Freeman MW, Kong XF, Schipani E, Urena P, Richards J, Bonventre JV, Potts JT Jr et al. (1992) Expression cloning of a common receptor for parathyroid hormone and parathyroid hormone-related peptide from rat osteoblast-like cells: a single receptor stimulates intracellular accumulation of both cAMP and inositol trisphosphates and increases intracellular-free calcium. Proc Natl Acad Sci USA 89(7):2732–2736

    Google Scholar 

  10. Gordeladze JO, Gautvik KM (1986) Hydroxycholecalciferols modulate parathyroid hormone and calcitonin-sensitive adenylyl cyclase in bone and kidney of rats. A possible physiological role for 24,25-dihydroxy vitamin D3. Biochem Pharmacol 35(6): 899–902

    Google Scholar 

  11. Jackowski S, Rettenmier CW, Sherr CJ, Rock CO (1986) A guanine nucleotide-dependent phosphatidylinositol 4,5-diphosphate phospholipase C in cells transformed by the v-fms and v-fes oncogenes. J Biol Chem 261:4978–4985

    Google Scholar 

  12. Engesæter LB, Ekeland A, Langeland N (1978) Methods for testing the mechanical properties of the rat femur. Acta Orthop Scand 49:512–518

    Google Scholar 

  13. Dahl E, Nordal KP, Halse J, Attramadal A (1988) Histomorphometric analysis of normal bone from the iliac crest of Norwegian subjects. Bone Miner 3:369–377

    Google Scholar 

  14. Parfitt AM, Glorieux FH, Kanis JA, Malluche H, Meunier PJ, Ott SM (1987) Bone histomorphometry nomenclature, symbols and units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res 2:595–610

    Google Scholar 

  15. Danielsen CC, Mosekilde Li, Andreassen TT (1992) Long-term effect of orchidectomy on cortical bone from rat femur: bone mass and mechanical properties. Calcif Tissue Int 50:169–174

    Google Scholar 

  16. Danielsen CC, Mosekilde Li, Svenstrup B (1993) Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution. Calcif Tissue Int 52:26–33

    Google Scholar 

  17. Oftebro H, Falch JA, Holmberg I, Haug E (1988) Validation of radioreceptor assay for 1,25-dihydroxyvitamin D using selected ion monitoring GC-MS. Clin Chim Acta 176:157–168

    Google Scholar 

  18. Gautvik KM, Teig V, Halvorsen JF, Arnesen E, Myhre L, Heimann P (1979) Development of sequence-specific radioimmunoassay of human parathyroid hormone and its use in the diagnosis of hyperparathyroidism. Scand J Clin Lab Invest 39:469–478

    Google Scholar 

  19. Gordeladze JO, Halse J, Djøseland O, Haugen HN (1978) A simple procedure for determination of hydroxyproline in urine and bone. Biochem Med Metab Biol 20:23–30

    Google Scholar 

  20. Sancho JJ, Duh QY, Oms L, Sitges-Serra A, Hammond ME, Arnaud CD, Clarc OH (1989) A new experimental model for secondary hyperparathyroidism. Surgery 106(6):1002–1008

    Google Scholar 

  21. Epstein S (1988) Serum and urinary markers of bone remodeling: assessment of bone turnover. Endocr Rew 9(4):437–449

    Google Scholar 

  22. Posen S, Lee C, Vines R (1977) Transient hyperphosphatasemia of infancy—an insufficiently recognized syndrome. Clin Chem 23(2):292–294

    Google Scholar 

  23. McComb RB, Bowers GN Jr, Posen S (1979) Serum alkaline phosphatase in patients with skeletal disorders: general consideration. In: Alkaline phosphatase. Plenum Press, New York, pp 570–571

    Google Scholar 

  24. Malluche HH, Smith AJ, Abreo K, Faugere MC (1984) The use of deferoxamine in the management of aluminium accumulation in bone in patients with renal failure. N Engl J Med 311(3):140–144

    Google Scholar 

  25. Deacon AC, Humle P, Hesp R, Green JR, Tellez M, Reeve J (1987) Estimation of whole body bone resorption rate: a comparison of urinary hydroxyproline excretion with two radioisotopic tracer methods in osteoporosis. Clin Chim Acta 166:297–306

    Google Scholar 

  26. Halse J, Gordeladze JO (1978) Urinary hydroxyproline excretion in acromegaly. Acta Endocrinol 89:483–491

    Google Scholar 

  27. Kivirikko KI (1970) Urinary excretion of hydroxyproline in health and disease. Int Rev Connect Tissue Res 15:93–163

    Google Scholar 

  28. Delmas PD (1990) Biochemical markers of bone turnover for clinical assessment of metabolic bone disease. Endocrinol Metab Clin North Am 19:1–18

    Google Scholar 

  29. Jouishomme H, Whitffield JR, Chakravarthy B, Durkin JP, Gagnon L, Isaacs RJ (1992) The protein kinase-C activation domain of the parathyroid hormone. Endocrinology 130(1):53–60

    Google Scholar 

  30. Fujimori A, Cheng S-L, Avioli LV, Civitelli R (1992) Structure-function relationship of parathryoid hormone: activation of phospholipase-C, protein kinase-A and-C in osteosarcoma cells. Endocrinology 130(1):29–36

    Google Scholar 

  31. Seitz PK, Nickols GA, Nickols MA, McPherson MB, Cooper CW (1990) Radioiodinated rat parathyroid hormone-(1-34) binds to its receptor on rat osteosarcoma cells in a manner consistent with two classes of binding sites. J Bone Miner Res 5(4):353–359

    Google Scholar 

  32. Cole JA, Carnes DL, Forte LR, Eber S, Poelling RE, Thorne PK (1989) Structure-activity relationships of parathyroid hormone analogs in the opossum kidney cell line. J Bone Miner Res 4(5):723–730

    Google Scholar 

  33. Quamme G, Pfeilschifter J, Murer H (1989) Parathyroid hormone inhibition of Na+/phosphate cotransport in OK cells: generation of second messengers in the regulatory cascade. Biochem Biophys Res Commun 1588(3):951–957

    Google Scholar 

  34. Klem KH, Jablonski G, Sæther O, Jarosz G, Gautvik KM, Gordeladze JO (1990) 1,25-dihydroxyvitamin D-3 and 24,25-dihydroxyvitamin D-3 affect parathormone (PTH)-sensitive adenylate cyclase activity and alkaline phosphatase secretion of osteoblastic cells through different mechanisms of action. Biochim Biophys Acta 1054:304–310

    Google Scholar 

  35. Mortensen BM, Gordeladze JO, Aksnes L, Gautvik KM (1990) Long-term administration of Vitamin D3 metabolites alters PTH-responsive osteoblastic adenylate cyclase in rats. Calcif Tissue Int 46:339–345

    Google Scholar 

  36. Gordeladze JO, Mortensen B, Nordal K, Halse J, Dahl E, Aksnes L, et al. (1987) The effect of parathyroid hormone (PTH) and 24,25-dihydroxy-vitamin D3 on adenylyl cyclase of iliac crest biopsies: diagnostic and prognostic tool for evaluation and treatment of uremic patients. Scand J Clin Lab Invest (suppl) 47(186):13–20

    Google Scholar 

  37. Berstein G, Blank JL, Smrcka AV, Higashijima T, Sternweis PC, Exton JH et al. (1992) Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified m1 muscarinic receptor, Gq/11, and phospholipase C-β1. J Biol Chem 267(12):8081–8088

    Google Scholar 

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Authors and Affiliations

  1. Institute of Medical Biochemistry, University of Oslo, Blindern, P.O. Box 1112, N-0317, Oslo, Norway

    G. Jablonski & J. O. Gordeladze

  2. Institute for Surgical Research, The National Hospital, Rikshospitalet, 0027, Oslo, Norway

    G. Jablonski & J. O. Gordeladze

  3. Department of Connective Tissue Biology, Institute of Anatomy, DK-8000, Aarhus C, Denmark

    C. C. Danielsen & L. Mosekilde

Authors
  1. G. Jablonski
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  2. C. C. Danielsen
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  3. L. Mosekilde
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  4. J. O. Gordeladze
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Jablonski, G., Danielsen, C.C., Mosekilde, L. et al. Surgically induced uremia in rats II: Osseous PTH-susceptible signaling systems as predictors of bone resorption. Calcif Tissue Int 55, 281–287 (1994). https://doi.org/10.1007/BF00310407

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  • DOI: https://doi.org/10.1007/BF00310407

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