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
September-2016 Volume 14 Issue 3

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
September-2016 Volume 14 Issue 3

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 Open Access

Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt

  • Authors:
    • Lin Zou
    • Guichun Zhang
    • Lifeng Liu
    • Chen Chen
    • Xuecheng Cao
    • Jinfang Cai
  • View Affiliations / Copyright

    Affiliations: Department of Traumatic Orthopedic Surgery, The General Hospital of Jinan Military Command, Jinan, Shandong 250031, P.R. China
    Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1915-1922
    |
    Published online on: July 1, 2016
       https://doi.org/10.3892/mmr.2016.5461
  • 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

Osteoblasts are critical in bone remodeling and the repair of bone fractures. Leptin is involved in bone metabolism and osteoblast survival through the downstream signaling pathway, however, the exact mechanism of the effect of leptin on osteoblasts remains to be fully elucidated. In the present study, hFOB 1.19 cells were used to observe the effects of leptin on cell proliferation and apoptosis, and to investigate the underlying mechanism. The results confirmed that treatment of hFOB 1.19 cells with leptin significantly induced cell proliferation. Western blot analysis showed that the expression of caveolin‑1 and the activation of Akt in the cells treated with leptin were significantly increased, compared with the control cells. Additionally, inhibiting Akt activation eliminated the effects on cell proliferation induced by leptin. The rates of cell apoptosis and cell cycle distribution were examined using flow cytometry, which revealed a decrease in the apoptotic rate and an increase in the proportion of cells in the S phase. This indicated that leptin was capable of inducing cell proliferation by inhibiting apoptosis and stimulating cell progression to the S phase. Transfection of the cells with caveolin‑1 small interfering RNA showed that the activation of Akt induced by leptin was significantly inhibited. Furthermore, caveolin‑1 knockdown and inhibiting Akt activation eliminated the increased proliferation, increased proportion of cells in the S phase and increased anti‑apoptotic effects induced by leptin. Taken together, the data obtained in the present study demonstrated that caveolin‑1 was critical in the proliferative effect of leptin on osteoblasts via the activation of Akt.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Sinha MK, Sturis J, Ohannesian J, Magosin S, Stephens T, Heiman ML, Polonsky KS and Caro JF: Ultradian oscillations of leptin secretion in humans. Biochem Biophys Res Commun. 228:733–738. 1996. View Article : Google Scholar : PubMed/NCBI

2 

Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S, et al: Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1:1155–1161. 1995. View Article : Google Scholar : PubMed/NCBI

3 

Zhang J and Wang N: Leptin in chronic kidney disease: A link between hematopoiesis, bone metabolism, and nutrition. Int Urol Nephrol. 46:1169–1174. 2014. View Article : Google Scholar

4 

Reseland JE, Syversen U, Bakke I, Qvigstad G, Eide LG, Hjertner O, Gordeladze JO and Drevon CA: Leptin is expressed in and secreted from primary cultures of human osteoblasts and promotes bone mineralization. J Bone Miner Res. 16:1426–1433. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Taichman RS and Hauschka PV: Effects of interleukin-1 beta and tumor necrosis factor-alpha on osteoblastic expression of osteocalcin and mineralized extracellular matrix in vitro. Inflammation. 16:587–601. 1992. View Article : Google Scholar : PubMed/NCBI

6 

Laharrague P, Larrouy D, Fontanilles AM, Truel N, Campfield A, Tenenbaum R, Galitzky J, Corberand JX, Pénicaud L and Casteilla L: High expression of leptin by human bone marrow adipocytes in primary culture. FASEB J. 12:747–752. 1998.PubMed/NCBI

7 

Zhang Y, Proenca R, Maffei M, Barone M, Leopold L and Friedman JM: Positional cloning of the mouse obese gene and its human homologue. Nature. 372:425–432. 1994. View Article : Google Scholar : PubMed/NCBI

8 

Sebastién-Ochoa A, Fernández-Garcia D, Reyes-García R, Mezquita-Raya P, Rozas-Moreno P, Alonso-Garcia G and Muñoz-Torres M: Adiponectin and leptin serum levels in osteoporotic postmenopausal women treated with raloxifene or alendronate. Menopause. 19:172–177. 2012. View Article : Google Scholar

9 

Lajeunesse D, Pelletier JP and Martel-Pelletier J: Osteoarthritis: A metabolic disease induced by local abnormal leptin activity? Curr Rheumatol Rep. 7:79–81. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Lee SW, Park MC, Park YB and Lee SK: Measurement of the serum leptin level could assist disease activity monitoring in rheumatoid arthritis. Rheumatol Int. 27:537–540. 2007. View Article : Google Scholar

11 

Wu YP, Chen WS, Xu SJ and Zhang N: Osteoporosis as a potential contributor to the bone metastases. Med Hypotheses. 75:514–516. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM and Karsenty G: Leptin inhibits bone formation through a hypothalamic relay: A central control of bone mass. Cell. 100:197–207. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Bartell SM, Rayalam S, Ambati S, Gaddam DR, Hartzell DL, Hamrick M, She JX, Della-Fera MA and Baile CA: Central (ICV) leptin injection increases bone formation, bone mineral density, muscle mass, serum IGF-1, and the expression of osteogenic genes in leptin-deficient ob/ob mice. J Bone Miner Res. 26:1710–1720. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Neve A, Corrado A and Cantatore FP: Osteoblast physiology in normal and pathological conditions. Cell Tissue Res. 343:289–302. 2011. View Article : Google Scholar

15 

Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P and Karsenty G: Leptin regulates bone formation via the sympathetic nervous system. Cell. 111:305–17. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Sawada N, Taketani Y, Amizuka N, Ichikawa M, Ogawa C, Nomoto K, Nashiki K, Sato T, Arai H, Isshiki M, et al: Caveolin-1 in extracellular matrix vesicles secreted from osteoblasts. Bone. 41:52–58. 2007. View Article : Google Scholar : PubMed/NCBI

17 

Zeidan A, Purdham DM, Rajapurohitam V, Javadov S, Chakrabarti S and Karmazyn M: Leptin induces vascular smooth muscle cell hypertrophy through angiotensin II- and endothelin-1-dependent mechanisms and mediates stretch-induced hypertrophy. J Pharmacol Exp Ther. 315:1075–1084. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Baker N, Zhang G, You Y and Tuan RS: Caveolin-1 regulates proliferation and osteogenic differentiation of human mesenchymal stem cells. J Cell Biochem. 113:3773–3787. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Solomon KR, Danciu TE, Adolphson LD, Hecht LE and Hauschka PV: Caveolin-enriched membrane signaling complexes in human and murine osteoblasts. J Bone Miner Res. 15:2380–2390. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Hens JR, Wilson KM, Dann P, Chen X, Horowitz MC and Wysolmerski JJ: TOPGAL mice show that the canonical Wnt signaling pathway is active during bone development and growth and is activated by mechanical loading in vitro. J Bone Miner Res. 20:1103–1113. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Forbes A, Wadehra M, Mareninov S, Morales S, Shimazaki K, Gordon LK and Braun J: The tetraspan protein EMP2 regulates expression of caveolin-1. J Biol Chem. 282:26542–26551. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Basu Roy UK, Henkhaus RS, Loupakis F, Cremolini C, Gerner EW and Ignatenko NA: Caveolin-1 is a novel regulator of K-RAS-dependent migration in colon carcinogenesis. Int J Cancer. 133:43–57. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-timequantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

24 

Liu GY, Liang QH, Cui RR, Liu Y, Wu SS, Shan PF, Yuan LQ and Liao EY: Leptin promotes the osteoblastic differentiation of vascular smooth muscle cells from female mice by increasing RANKL expression. Endocrinology. 155:558–567. 2014. View Article : Google Scholar

25 

Li Z, Shen J, Wu WK, Yu X, Liang J, Qiu G and Liu J: Leptin induces cyclin D1 expression and proliferation of human nucleus pulposus cells via JAK/STAT, PI3K/Akt and MEK/ERK pathways. PLoS One. 7:e531762012. View Article : Google Scholar

26 

Beaulieu A, Poncin G, Belaid-Choucair Z, Humblet C, Bogdanovic G, Lognay G, Boniver J and Defresne MP: Leptin reverts pro-apoptotic and antiproliferative effects of α-linolenic acids in BCR-ABL positive leukemic cells: Involvement of PI3K pathway. PLoS One. 6:e256512011. View Article : Google Scholar

27 

Lloyd JT, Alley DE, Hawkes WG, Hochberg MC, Waldstein SR and Orwig DL: Body mass index is positively associated with bone mineral density in US older adults. Arch Osteoporos. 9:1752014. View Article : Google Scholar : PubMed/NCBI

28 

Frankenberry KA, Somasundar P, McFadden DW and Vona-Davis LC: Leptin induces cell migration and the expression of growth factors in human prostate cancer cells. Am J Surg. 188:560–565. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Tsuchiya T, Shimizu H, Horie T and Mori M: Expression of leptin receptor in lung: Leptin as a growth factor. Eur J Pharmacol. 365:273–279. 1999. View Article : Google Scholar : PubMed/NCBI

30 

Gordeladze JO, Drevon CA, Syversen U and Reseland JE: Leptin stimulates human osteoblastic cell proliferation, de novo collagen synthesis, and mineralization: Impact on differentiation markers, apoptosis, and osteoclastic signaling. J Cell Biochem. 85:825–836. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Lee YJ, Park JH, Ju SK, You KH, Ko JS and Kim HM: Leptin receptor isoform expression in rat osteoblasts and their functional analysis. FEBS Lett. 528:43–47. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Zhang J, Lazarenko OP, Blackburn ML, Badger TM, Ronis MJ and Chen JR: Soy protein isolate down-regulates caveolin-1 expression to suppress osteoblastic cell senescence pathways. FASEB J. 28:3134–3145. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Singh P, Peterson TE, Sert-Kuniyoshi FH, Jensen MD and Somers VK: Leptin upregulates caveolin-1 expression: Implications for development of atherosclerosis. Atherosclerosis. 217:499–502. 2011. View Article : Google Scholar

34 

Jasmin JF, Mercier I, Sotgia F and Lisanti MP: SOCS proteins and caveolin-1 as negative regulators of endocrine signaling. Trends Endocrinol Metab. 17:150–158. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Razani B, Woodman SE and Lisanti MP: Caveolae: From cell biology to animal physiology. Pharmacol Rev. 54:431–467. 2002. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zou L, Zhang G, Liu L, Chen C, Cao X and Cai J: Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt. Mol Med Rep 14: 1915-1922, 2016.
APA
Zou, L., Zhang, G., Liu, L., Chen, C., Cao, X., & Cai, J. (2016). Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt. Molecular Medicine Reports, 14, 1915-1922. https://doi.org/10.3892/mmr.2016.5461
MLA
Zou, L., Zhang, G., Liu, L., Chen, C., Cao, X., Cai, J."Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt". Molecular Medicine Reports 14.3 (2016): 1915-1922.
Chicago
Zou, L., Zhang, G., Liu, L., Chen, C., Cao, X., Cai, J."Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt". Molecular Medicine Reports 14, no. 3 (2016): 1915-1922. https://doi.org/10.3892/mmr.2016.5461
Copy and paste a formatted citation
x
Spandidos Publications style
Zou L, Zhang G, Liu L, Chen C, Cao X and Cai J: Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt. Mol Med Rep 14: 1915-1922, 2016.
APA
Zou, L., Zhang, G., Liu, L., Chen, C., Cao, X., & Cai, J. (2016). Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt. Molecular Medicine Reports, 14, 1915-1922. https://doi.org/10.3892/mmr.2016.5461
MLA
Zou, L., Zhang, G., Liu, L., Chen, C., Cao, X., Cai, J."Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt". Molecular Medicine Reports 14.3 (2016): 1915-1922.
Chicago
Zou, L., Zhang, G., Liu, L., Chen, C., Cao, X., Cai, J."Caveolin-1 is critical in the proliferative effect of leptin on osteoblasts through the activation of Akt". Molecular Medicine Reports 14, no. 3 (2016): 1915-1922. https://doi.org/10.3892/mmr.2016.5461
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