Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2016 Volume 13 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2016 Volume 13 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation

  • Authors:
    • Haitao He
    • Jianshen Chai
    • Shengfu Zhang
    • Linlin Ding
    • Peng Yan
    • Wenjun Du
    • Zhenzhou Yang
  • View Affiliations / Copyright

    Affiliations: Department of Maxillofacial and Head and Neck Surgery, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, P.R. China, Department of Oncology, Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, P.R. China
  • Pages: 3977-3984
    |
    Published online on: March 21, 2016
       https://doi.org/10.3892/mmr.2016.5023
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Calcitonin-gene-related peptide (CGRP) is a neuropeptide, which is widely distributed throughout the central and peripheral nervous systems. Numerous mechanisms underlying the action of CGRP in osteoblast-associated cells have been suggested for bone growth and metabolism. The present study was designed to closely investigate the osteoblast‑ and osteoclast-associated mechanisms of the effect of CGRP administration on bone metabolism in primary osteoblasts. Primary osteoblasts were obtained from newborn rabbit calvaria and incubated with different concentrations of human CGRP (hCGRP), hCGRP and hCGRP (8‑37), or without treatment as a control. Intracellular calcium (Ca2+) and cyclic adenosine monophosphate (cAMP) were detected following treatment, as well as the expression levels of osteoblast differentiation markers, including activating transcription factor‑4 (ATF4) and osteocalcin (OC), and receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG). The isolated primary osteoblasts were found to stain positively for ALP. hCGRP treatment had no significant effect on transient intracellular Ca2+ in the osteoblasts. Treatment of the osteoblasts with hCGRP led to elevations in the expression levels of cAMP, ATF4 and OPG, and downregulation in the expression of RANKL, in a dose‑dependent manner. These effects were markedly reversed by the addition of hCGRP (8‑37). The results of the present study demonstrated that CGRP administration not only stimulated osteoblast differentiation, as demonstrated by upregulated expression levels of ATF4 and OC in the hCGRP‑treated osteoblasts, but also inhibited OPG/RANKL‑regulated osteoclastogenesis. CGRP may act as a modulator of bone metabolism through osteoblast and osteoclast-associated mechanisms, which result in osteoblast formation with subsequent activation of bone formation.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Offley SC, Guo TZ, Wei T, Clark JD, Vogel H, Lindsey DP, Jacobs CR, Yao W, Lane NE and Kingery WS: Capsaicin-sensitive sensory neurons contribute to the maintenance of trabecular bone integrity. J Bone Miner Res. 20:257–267. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Irie K, Hara-Irie F, Ozawa H and Yajima T: Calcitonin gene-related peptide (CGRP)-containing nerve fibers in bone tissue and their involvement in bone remodeling. Microsc Res Tech. 58:85–90. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Sample SJ, Heaton CM, Behan M, Bleedom JA, Racette MA, Hao Z and Muir P: Role of calcitonin gene-related peptide in functional adaptation of the skeleton. PLoS One. 9:e1139592014. View Article : Google Scholar : PubMed/NCBI

4 

Villa I, Melzi R, Pagani F, Ravasi F, Rubinacci A and Guidobono F: Effects of calcitonin gene-related peptide and amylin on human osteoblast-like cells proliferation. Eur J Pharmacol. 409:273–278. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Ballica R, Valentijn K, Khachatryan A, Guerder S, Kapadia S, Gundberg C, Gilligan J, Flavell RA and Vignery A: Targeted expression of calcitonin gene-related peptide to osteoblasts increases bone density in mice. J Bone Miner Res. 14:1067–1074. 1999. View Article : Google Scholar : PubMed/NCBI

6 

Valentijn K, Gutow AP, Troiano N, Gundberg C, Gilligan JP and Vignery A: Effects of calcitonin gene-related peptide on bone turnover in ovariectomized rats. Bone. 21:269–274. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Schinke T, Liese S, Priemel M, Haberland M, Schilling AF, Catala-Lehnen P, Blicharski D, Rueger JM, Gagel RF, Emeson RB and Amling M: Decreased bone formation and osteopenia in mice lacking alpha-calcitonin gene-related peptide. J Bone Miner Res. 19:2049–2056. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Villa I, Mrak E, Rubinacci A, Ravasi F and Guidobono F: CGRP inhibits osteoprotegerin production in human osteoblast-like cells via cAMP/PKA-dependent pathway. Am J Physiol Cell Physiol. 291:C529–C537. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Villa I, Dal Fiume C, Maestroni A, Rubinacci A, Ravasi F and Guidobono F: Human osteoblast-like cell proliferation induced by calcitonin-related peptides involves PKC activity. Am J Physiol Endocrinol Metab. 284:E627–E633. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Naot D and Cornish J: The role of peptides and receptors of the calcitonin family in the regulation of bone metabolism. Bone. 43:813–818. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Bo Y, Yan L, Gang Z, Tao L and Yinghui T: Effect of calcitonin gene-related peptide on osteoblast differentiation in an osteoblast and endothelial cell co-culture system. Cell Biol Int. 36:909–915. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Drissi H, Lieberherr M, Hott M, Marie PJ and Lasmoles F: Calcitonin gene-related peptide (CGRP) increases intracellular free Ca2+ concentrations but not cyclic AMP formation in CGRP receptor-positive osteosarcoma cells (OHS-4). Cytokine. 11:200–207. 1999. View Article : Google Scholar : PubMed/NCBI

13 

Matsuo K and Irie N: Osteoclast-osteoblast communication. Arch Biochem Biophys. 473:201–209. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, et al: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 93:165–176. 1998. View Article : Google Scholar : PubMed/NCBI

15 

Yoo YM, Kwag JH, Kim KH and Kim CH: Effects of neuropeptides and mechanical loading on bone cell resorption in vitro. Int J Mol Sci. 15:5874–5883. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Kauther MD, Xu J and Wedemeyer C: Alpha-calcitonin gene-related peptide can reverse the catabolic influence of UHMWPE particles on RANKL expression in primary human osteoblasts. Int J Biol Sci. 6:525–536. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Zhang Y, Sun X, Sun G, Liu S and Wang L: DNA damage induced by fluoride in rat osteoblasts. Fluoride. 39:191–194. 2006.

18 

Li SH, Guo DZ, Li B, Yin HB, Li JK, Xiang JM and Deng GZ: The stimulatory effect of insulin-like growth factor-1 on the proliferation, differentiation and mineralisation of osteoblastic cells from Holstein cattle. Vet J. 179:430–436. 2009. View Article : Google Scholar

19 

Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI

20 

Yu HT, Yu M, Li CY, Zhan YQ, Xu WX, Li YH, Li W, Wang ZD, Ge CH and Yang XM: Specific expression and regulation of hepassocin in the liver and down-regulation of the correlation of HNF1alpha with decreased levels of hepassocin in human hepatocellular carcinoma. J Biol Chem. 284:13335–13347. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Chomczynski P and Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 162:156–159. 1987. View Article : Google Scholar : PubMed/NCBI

22 

Vignery A and McCarthy TL: The neuropeptide calcitonin gene-related peptide stimulates insulin-like growth factor I production by primary fetal rat osteoblasts. Bone. 18:331–335. 1996. View Article : Google Scholar : PubMed/NCBI

23 

Tian G, Zhang G and Tan YH: Calcitonin gene-related peptide stimulates BMP-2 expression and the differentiation of human osteoblast-like cells in vitro. Acta Pharmacol Sin. 34:1467–1474. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Kawase T, Howard GA, Roos BA and Burns DM: Diverse actions of calcitonin gene-related peptide on intracellular free Ca2+ concentrations in UMR 106 osteoblastic cells. Bone. 16(Suppl 4): S379–S384. 1995. View Article : Google Scholar

25 

Bjurholm A, Kreicbergs A, Brodin E and Schultzberg M: Substance P- and CGRP-immunoreactive nerves in bone. Peptides. 9:165–171. 1988. View Article : Google Scholar : PubMed/NCBI

26 

Tippins JR, Morris HR, Panico M, Etienne T, Bevis P, Girgis S, MacIntyre I, Azria M and Attinger M: The myotropic and plasma-calcium modulating effects of calcitonin gene-related peptide (CGRP). Neuropeptides. 4:425–434. 1984. View Article : Google Scholar : PubMed/NCBI

27 

Burns DM, Stehno-Bittel L and Kawase T: Calcitonin gene-related peptide elevates calcium and polarizes membrane potential in MG-63 cells by both cAMP-independent and-dependent mechanisms. Am J Physiol Cell Physiol. 287:C457–C467. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Katafuchi T, Kikumoto K, Hamano K, Kangawa K, Matsuo H and Minamino N: Calcitonin receptor-stimulating peptide, a new member of the calcitonin gene-related peptide family its isolation from porcine brain, structure, tissue distribution and biological activity. J Biol Chem. 278:12046–12054. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Born W, Fischer JA and Muff R: Receptors for calcitonin gene-related peptide, adrenomedullin and amylin: The contributions of novel receptor-activity-modifying proteins. Receptors Channels. 8:201–209. 2002. View Article : Google Scholar

30 

Lian N, Lin T, Liu W, Wang W, Li L, Sun S, Nyman JS and Yang X: Transforming growth factor β suppresses osteoblast differentiation via the vimentin activating transcription factor 4 (ATF4) axis. J Biol Chem. 287:35975–35984. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka HC, Schinke T, Li L, Brancorsini S, Sassone-Corsi P, Townes TM, et al: ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: Implication for Coffin-Lowry Syndrome. Cell. 117:387–398. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Luo J, Zhou W, Zhou X, Li D, Weng J, Yi Z, Cho SG, Li C, Yi T, Wu X, et al: Regulation of bone formation and remodeling by G-protein-coupled receptor 48. Development. 136:2747–2756. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Angelopoulos NG, Goula A, Katounda E, Rombopoulos G, Kaltzidou V, Kaltsas D, Malaktari S, Athanasiou V and Tolis G: Circulating osteoprotegerin and receptor activator of NF-kappaB ligand system in patients with beta-thalassemia major. J Bone Miner Metab. 25:60–67. 2007. View Article : Google Scholar

34 

Wang L, Shi X, Zhao R, Halloran BP, Clark DJ, Jacobs CR and Kingery WS: Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-kappaB activation, osteoclastogenesis and bone resorption. Bone. 46:1369–1379. 2010. View Article : Google Scholar :

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
He H, Chai J, Zhang S, Ding L, Yan P, Du W and Yang Z: CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation. Mol Med Rep 13: 3977-3984, 2016.
APA
He, H., Chai, J., Zhang, S., Ding, L., Yan, P., Du, W., & Yang, Z. (2016). CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation. Molecular Medicine Reports, 13, 3977-3984. https://doi.org/10.3892/mmr.2016.5023
MLA
He, H., Chai, J., Zhang, S., Ding, L., Yan, P., Du, W., Yang, Z."CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation". Molecular Medicine Reports 13.5 (2016): 3977-3984.
Chicago
He, H., Chai, J., Zhang, S., Ding, L., Yan, P., Du, W., Yang, Z."CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation". Molecular Medicine Reports 13, no. 5 (2016): 3977-3984. https://doi.org/10.3892/mmr.2016.5023
Copy and paste a formatted citation
x
Spandidos Publications style
He H, Chai J, Zhang S, Ding L, Yan P, Du W and Yang Z: CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation. Mol Med Rep 13: 3977-3984, 2016.
APA
He, H., Chai, J., Zhang, S., Ding, L., Yan, P., Du, W., & Yang, Z. (2016). CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation. Molecular Medicine Reports, 13, 3977-3984. https://doi.org/10.3892/mmr.2016.5023
MLA
He, H., Chai, J., Zhang, S., Ding, L., Yan, P., Du, W., Yang, Z."CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation". Molecular Medicine Reports 13.5 (2016): 3977-3984.
Chicago
He, H., Chai, J., Zhang, S., Ding, L., Yan, P., Du, W., Yang, Z."CGRP may regulate bone metabolism through stimulating osteoblast differentiation and inhibiting osteoclast formation". Molecular Medicine Reports 13, no. 5 (2016): 3977-3984. https://doi.org/10.3892/mmr.2016.5023
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team