Skip to main content

Advertisement

SpringerLink
Log in

Responsiveness of gene expression markers of osteoblastic and osteoclastic activity to calcitonin in the appendicular and axial skeleton of the rat in vivo

  • Molecular and Cellular Biology
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

We have previously shown that calcitonin (CT), an inhibitor of bone resorption, increases vertebral, but not femoral bone density in the rat [3]. To address the physiologic responses associated with these effects on bone mineral density (BMD), we assessed mRNA transcripts reflecting activities of osteoblasts (type I collagen, osteocalcin, osteopontin, and alkaline phosphatase), osteoclasts [tartrate-resistant acid phosphatase (TRAP)], and cell proliferation (histone H4) in the spine and femur of these rats. CT increased spine BMD while increasing type I collagen and decreasing TRAP and histone mRNAs. In the femur, where CT had no effect on BMD, it decreased type I collagen and histone H4 mRNA but did not affect TRAP. CT had no effect on the gene expression of osteocalcin, osteopontin, or alkaline phosphatase at either site. The results indicate that selective alterations in gene expression, as reflected by steady state mRNA levels, are consistent with the changes observed by BMD measurement, and can more clearly define the specific contribution from osteoblast and osteoclast activity. This study demonstrates a heterogeneity in response of the axial and appendicular skeleton to CT, reflected by alterations in gene expression that provide a basis for understanding the observed BMD responses to various pharmacologic interventions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ninomiya J, Tracy R, Calore J, Gendreau MA, Kelm RJ, Mann KG (1990) Heterogeneity of human bone. J Bone Miner Res 5:933–938

    Google Scholar 

  2. Civitelli R, Gonnelli S, Zacchei F, Bigazzi S, Vattimo A, Avioli L, Gennari C (1988) Bone turnover in postmenopausal osteoporosis. Effect of calcitonin treatment. J Clin Invest 82:1268–1274

    Google Scholar 

  3. Ongphiphadhanakul B, Alex S, Braverman LE, Baran DT (1992) Excessive L-thyroxin-therapy decreases femoral bone mineral densities in the rat: effect of hypogonadism and calcitonin. J Bone Miner Res 7:1227–1231

    Google Scholar 

  4. Shalhoub V, Jackson M, Lian J, Stein G, Marks S (1991) Gene expression during skeletal development in three osteopetrotic rat mutations. J Biol Chem 266:9847–9856

    Google Scholar 

  5. Turner R, Colvard D, Spelsberg T (1991) Measurement of mRNA levels in the periosteum of aging rats. Cells Materials (suppl) 1:47–51

    Google Scholar 

  6. Turner R, Spelsberg T (1991) Correlation between mRNA levels for bone cell proteins and bone formation in long bones of maturing rats. Am J Physiol 261:E348-E353

    Google Scholar 

  7. Ongphiphadhanakul B, Jenis LG, Braverman LE, Alex S, Stein GS, Lian JB, Baran DT (1993) Etidornate inhibits the thyroid hormone-induced bone loss in rats assessed by bone mineral density and messenger ribonucleic acid markers of osteoblast and osteoclast function. Endocrinology 133:2502–2507

    Google Scholar 

  8. Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter W (1979) Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18:5294–5299

    Google Scholar 

  9. Feinberg A, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to a high specific activity. Anal Biochem 132:6–13

    Google Scholar 

  10. Lian J, Stewart C, Puchacz E, Mackoviak S, Shalhoub V, Collart D, Zambetti G, Stein G (1989) Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. Proc Natl Acad Sci USA 86:1143–1147

    Google Scholar 

  11. Genovese C, Rowe D, Kream B (1984) Construction of DNA sequences complementary to rat 1 and 2 collagen mRNA and their use in studying the regulation of type I collagen synthesis by 1,25-dihydroxyvitamin D. Biochemistry 23:6210–6216

    Google Scholar 

  12. Grimes S, Weisz-Carrington P, Daum H, Green L, Wright K, Stein G, Stein J (1987) A rat histone H4 gene closely associated with the testis-specific H1t gene. Exp Cell Res 173:534–545

    Google Scholar 

  13. Oldberg A, Franzen A, Heinegard D (1986) Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an arg-gly-asp cell-binding sequence. Proc Natl Acad Sci USA 83:8819–8823

    Google Scholar 

  14. Noda M, Yoon K, Thiede M, Buenaga R, Weiss M, Henthorn P, Harris H, Rodan G (1987) cDNA cloning of alkaline phosphatase from rat osteosarcoma (ROS 17/2.8) cells. J Bone Miner Res 2:161–164

    Google Scholar 

  15. Ketcham C, Roberts R, Simmden R, Nick H (1989) Molecular cloning of the type 5, iron-containing, tartrate-resistant acid phosphatase from human placenta. J Biol Chem 264:557–563

    Google Scholar 

  16. Wilson G, Hollar B, Waterson J, Schmickel R (1976) Molecular analysis of cloned human 18s ribosomal DNA segments. Proc Natl Acad Sci USA 75:5367–5371

    Google Scholar 

  17. Mazzuoli G, Passeri M, Gennari G, Minisola S, Antonell R, Valtorta C, Palummeri F, Cervellini G, Gonnelli S, Francini G (1986) Effects of salmon calcitonin in postmenopausal osteoporosis: a controlled double-blind clinical study. Calcif Tissue Int 38:3–8

    Google Scholar 

  18. Avioli L (1991) Heterogeneity of osteoporotic syndromes and the response to calcitonin therapy. Calcif Tissue Int 49(suppl 2):S16-S19

    Google Scholar 

  19. Nakatsuka K, Nishizawa Y, Hagiwara S, Koyama H, Miki T, Ochi H, Morii H (1990) Effect of calcitonin on total body bone mineral contents of experimental osteoporotic rats determined by dual photon absorptiometry. Calcif Tissue Int 47:378–382

    Google Scholar 

  20. Weiss RE, Singer FR, Gorn AH, Hofer DP, Mimni ME (1981) Calcitonin stimulates bone formation when administered prior to initiation of osteogenesis. J Clin Invest 68:815–818

    Google Scholar 

  21. Lerner UH, Ransjo M, Klaushofer K, Horandner H, Hoffmann O, Czerwenka E, Koller K, Perterlik M (1989) Comparison between the effects of forskolin and calcitonin on bone resorption and osteoclastic morphology in vitro. Bone 10:377–387

    Google Scholar 

  22. Nicholson G, Mosely JM, Sexton PM, Mendelsohn F, Martin T (1986) Abundant calcitonin receptors in isolated rat osteoclasts. Biochemical and autoradiographic characterization. J Clin Invest 78:355–360

    Google Scholar 

  23. Chambers T, Magnus C (1982) Calcitonin alters behavior of isolated osteoclasts. J Pathol 136:27–39

    Google Scholar 

  24. Yumita S, Nicholson G, Rowe D, Kent G, Martin T (1991) Biphasic effect of calcitonin on tartrate-resistant acid phosphatase activity in isolated rat osteoclasts. J Bone Miner Res 6:591–597

    Google Scholar 

  25. Morel G, Boivin G, David L, Dubois PM, Meunier PJ (1985) Immunocytochemical evidence for endogenous calcitonin and parathyroid hormone in osteoblasts from the calvaria of neonatal mice. Calcif Tissue Int 240:89–93

    Google Scholar 

  26. Rao LG, Heersche JNM, Marchuk LL, Sturtridge W (1981) Immunohistochemical demonstration of calcitonin binding to specific cell types in fixed rat bone tissue. Endocrinology 108: 1972–1978

    Google Scholar 

  27. Farley JR, Tarbaux NM, Hall SL, Linkhart TA, Baylink DJ (1988) The anti-bone-resorptive agent calcitonin also acts in vitro to directly increase bone formation and bone cell proliferation. Endocrinology 123:159–167

    Google Scholar 

  28. Farley JR, Tarbaux NM, Vermeiden JPW, Baylink DJ (1988) In vitro evidence that local and systemic skeletal effectors can regulate 3H-thymidine incorporation in chick calvarial cell cultures and modulate the stimulatory action(s) of embryonic chick bone extract. Calcif Tissue Int 42:23–33

    Google Scholar 

  29. Farley JR, Hall SL, Tarbaux NM (1989) Calcitonin (but not calcitonin gene-related peptide) increases mouse bone cell proliferation in a dose-dependent manner, and increases mouse bone formation alone and in combination with fluoride. Calcif Tissue Int 45:214–221

    Google Scholar 

  30. Farley JR, Wergedal JE, Hall SL, Herring S, Tarbaux NM (1991) Calcitonin has direct effects on 3H-thymidine incorporation and alkaline phosphatase activity in human osteoblast-like cells. Calcif Tissue Int 48:297–301

    Google Scholar 

  31. Ito N, Yamazaki H, Nakazaki M, Miyahara T, Kozuka H, Sudo H (1987) Response of osteoblastic clonal cell line (MC3T3-E1) to (Asu1.7) eel calcitonin at a specific cell density or differentiation state. Calcif Tissue Int 40:200–205

    Google Scholar 

  32. Iida-Klein A, Yee DC, Brandli DW, Mirikitani EJM, Hahn TG (1992) Effects of calcitonin on 31, 51-cyclic adenosine monophosphate and calcium second messenger generation and osteoblast function in UMR 106-06 osteoblast-like cells. Endocrinology 130:381–388

    Google Scholar 

  33. Forrest SM, Ng KW, Findlay DM, Michelangeli VP, Livesey SA, Partridge NC, Zajac JD, Martin TJ (1985) Characterization of an osteoblast-like clonal cell line which responds to both parathyroid hormone and calcitonin. Calcif Tissue Int 37:51–56

    Google Scholar 

  34. Ferrier J, Ward-Kesthely A, Heersche JNW, Aubin JE (1988) Membrane potential changes, cAMP stimulation and contraction in osteoblast-like UMR 106 cells in response to calcitonin and parathyroid hormone. Bone Miner 4:133–145

    Google Scholar 

  35. Ferrier J, Kesthely A, Xia S-L (1992) Hormone responses of in vitro bone nodule cells: studies on changes of intracellular calcium and membrane potential in response to parathyroid hormone and calcitonin. Bone Miner 19:103–116

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopedics, University of Massachusetts Medical Center, 55 Lake Avenue North, 01655, Worcester, Massachusetts

    L. G. Jenis & D. T. Baran

  2. Division of Endocrinology, University of Massachusetts Medical Center, 01655, Worcester, Massachusetts

    B. Ongphiphadhanakul, L. E. Braverman & D. T. Baran

  3. Department of Pharmacology, University of Massachusetts Medical Center, 01655, Worcester, Massachusetts

    R. Lew

  4. Department of Cell Biology, University of Massachusetts Medical Center, 01655, Worcester, Massachusetts

    G. S. Stein, J. B. Lian & D. T. Baran

Authors
  1. L. G. Jenis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Ongphiphadhanakul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. E. Braverman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. S. Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. B. Lian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Lew
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. T. Baran
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jenis, L.G., Ongphiphadhanakul, B., Braverman, L.E. et al. Responsiveness of gene expression markers of osteoblastic and osteoclastic activity to calcitonin in the appendicular and axial skeleton of the rat in vivo . Calcif Tissue Int 54, 511–515 (1994). https://doi.org/10.1007/BF00334334

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00334334

Key words

Search

Navigation