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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
March-2016 Volume 37 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
March-2016 Volume 37 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

Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation

  • Authors:
    • Feng Lin
    • Wei Zhang
    • Deting Xue
    • Ting Zhu
    • Jin Li
    • Erman Chen
    • Xueyu Yao
    • Zhijun Pan
  • View Affiliations / Copyright

    Affiliations: Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
  • Pages: 789-797
    |
    Published online on: February 3, 2016
       https://doi.org/10.3892/ijmm.2016.2479
  • 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

High mobility group box 1 (HMGB1) epxression has been found in the inflammatory microenvironment of fractures. It is well known that HMGB1 acts as a chemoattractant for mesenchymal stem cells (MSCs); however, the effects of HMGB1 on MSC migration and osteoblastic differentiation, and the signaling pathways involved in these effects, have not yet been elucidated. In this study, we aimed to investigate these effects, as well as the signaling mechanisms involved, using in vitro models. We found that HMGB1, in varying concentrations, promoted the osteoblastic differentiation of MSCs, the synthesis of receptor for advanced glycation end products (RAGE) and Toll-like receptor (TLR)2/4, and the activation of the p38 mitogen-activated protein kinase (MAPK) and nuclear factor‑κB (NF‑κB) signaling pathways. Subsequently, we cultured the MSCs in the appropriate concentration of HMGB1, and determined the signaling pathways involved in the effects of HMGB1 on MSC migration and differentiation, using receptor neutralizing antibodies and signaling pathway inhibitors. From the results of this study, we concluded that HMGB1 promotes MSC migration through the activation of the p38 MAPK signaling pathway, and also promotes MSC differentiation by binding to TLR2/4 and activating the p38 MAPK signaling pathway. These findings elucidate the mechanisms underlying the effects of HMGB1 in the fracture microenvironment, which may provide a theoretical basis for the development of improved clinical treatments for fractures.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Degryse B, Bonaldi T, Scaffidi P, Müller S, Resnati M, Sanvito F, Arrigoni G and Bianchi ME: The high mobility group (HMG) boxes of the nuclear protein HMG1 induce chemotaxis and cytoskeleton reorganization in rat smooth muscle cells. J Cell Biol. 152:1197–1206. 2001. View Article : Google Scholar : PubMed/NCBI

2 

Palumbo R, Sampaolesi M, De Marchis F, Tonlorenzi R, Colombetti S, Mondino A, Cossu G and Bianchi ME: Extracellular HMGB1, a signal of tissue damage, induces mesoangioblast migration and proliferation. J Cell Biol. 164:441–449. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Andersson U, Erlandsson-Harris H, Yang H and Tracey KJ: HMGB1 as a DNA-binding cytokine. J Leukoc Biol. 72:1084–1091. 2002.PubMed/NCBI

4 

Yang H, Wang H, Czura CJ and Tracey KJ: HMGB1 as a cytokine and therapeutic target. J Endotoxin Res. 8:469–472. 2002. View Article : Google Scholar

5 

Granero-Moltó F, Weis JA, Miga MI, Landis B, Myers TJ, O'Rear L, Longobardi L, Jansen ED, Mortlock DP and Spagnoli A: Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells. 27:1887–1898. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Glass GE, Chan JK, Freidin A, Feldmann M, Horwood NJ and Nanchahal J: TNF-alpha promotes fracture repair by augmenting the recruitment and differentiation of muscle-derived stromal cells. Proc Natl Acad Sci USA. 108:1585–1590. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Marsell R and Einhorn TA: The biology of fracture healing. Injury. 42:551–555. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Naglova H and Bucova M: HMGB1 and its physiological and pathological roles. Bratisl Lek Listy. 113:163–171. 2012.PubMed/NCBI

9 

Meng E, Guo Z, Wang H, Jin J, Wang J, Wang H, Wu C and Wang L: High mobility group box 1 protein inhibits the proliferation of human mesenchymal stem cells and promotes their migration and differentiation along osteoblastic pathway. Stem Cells Dev. 17:805–813. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A and Abraham E: Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem. 279:7370–7377. 2004. View Article : Google Scholar

11 

Nakajima Y, Inagaki Y, Kido J and Nagata T: Advanced glycation end products increase expression of S100A8 and A9 via RAGE-MAPK in rat dental pulp cells. Oral Dis. 21:328–334. 2015. View Article : Google Scholar

12 

Hu Y, Chan E, Wang SX and Li B: Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation. Endocrinology. 144:2068–2074. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Chang CP, Su YC, Lee PH and Lei HY: Targeting NFKB by autophagy to polarize hepatoma-associated macrophage differentiation. Autophagy. 9:619–621. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Delhalle S, Blasius R, Dicato M and Diederich M: A beginner's guide to NF-kappaB signaling pathways. Ann N Y Acad Sci. 1030:1–13. 2004. View Article : Google Scholar

15 

Wang H, Vishnubhakat JM, Bloom O, Zhang M, Ombrellino M, Sama A and Tracey KJ: Proinflammatory cytokines (tumor necrosis factor and interleukin 1) stimulate release of high mobility group protein-1 by pituicytes. Surgery. 126:389–392. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Guo Z, Li H, Li X, Yu X, Wang H, Tang P and Mao N: In vitro characteristics and in vivo immunosuppressive activity of compact bone-derived murine mesenchymal progenitor cells. Stem Cells. 24:992–1000. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Yuk JM, Yang CS, Shin DM, Kim KK, Lee SK, Song YJ, Lee HM, Cho CH, Jeon BH and Jo EK: A dual regulatory role of apurinic/apyrimidinic endonuclease 1/redox factor-1 in HMGB1-induced inflammatory responses. Antioxid Redox Signal. 11:575–588. 2009. View Article : Google Scholar

18 

Kim JB, Sig Choi J, Yu YM, Nam K, Piao CS, Kim SW, Lee MH, Han PL, Park JS and Lee JK: HMGB1, a novel cytokine-like mediator linking acute neuronal death and delayed neuroinflammation in the postischemic brain. J Neurosci. 26:6413–6421. 2006. View Article : Google Scholar : PubMed/NCBI

19 

Wang XB, Chen X, Song KD, Wang J, Yao W, Liu HL and Sun ZM: Effects of HMGB1 on human cord blood CD34(+) hematopoietic stem cells proliferation and differentiation in vitro. Zhonghua Xue Ye Xue Za Zhi. 31:88–91. 2010.In Chinese. PubMed/NCBI

20 

Polanská E, Dobšáková Z, Dvořáčková M, Fajkus J and Štros M: HMGB1 gene knockout in mouse embryonic fibroblasts results in reduced telomerase activity and telomere dysfunction. Chromosoma. 121:419–431. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Tang Q, Li J, Zhu H, Li P, Zou Z and Xiao Y: Hmgb1-IL-23-IL-17-IL-6-Stat3 axis promotes tumor growth in murine models of melanoma. Mediators Inflamm. 2013:7138592013. View Article : Google Scholar

22 

Bianchi ME and Manfredi AA: High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev. 220:35–46. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Sun W, Jiao Y, Cui B, Gao X, Xia Y and Zhao Y: Immune complexes activate human endothelium involving the cell-signaling HMGB1-RAGE axis in the pathogenesis of lupus vasculitis. Lab Invest. 93:626–638. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Zhang M, Sun L, Wang X, Chen S, Jia Q, Liu N, Chen Y, Kong Y, Zhang L and Zhang AL: Activin B promotes BM-MSC-mediated cutaneous wound healing by regulating cell migration via the JNK-ERK signaling pathway. Cell Transplant. 23:1061–1073. 2014. View Article : Google Scholar

25 

Akira S, Hirano T, Taga T and Kishimoto T: Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 4:2860–2867. 1990.PubMed/NCBI

26 

Schilling D, Thomas K, Nixdorff K, Vogel SN and Fenton MJ: Toll-like receptor 4 and Toll-IL-1 receptor domain-containing adapter protein (TIRAP)/myeloid differentiation protein 88 adapter-like (Mal) contribute to maximal IL-6 expression in macrophages. J Immunol. 169:5874–5880. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Pevsner-Fischer M, Morad V, Cohen-Sfady M, Rousso-Noori L, Zanin-Zhorov A, Cohen S, Cohen IR and Zipori D: Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood. 109:1422–1432. 2007. View Article : Google Scholar

28 

Liu Y, Han D, Wang L and Feng H: Down-regulation of Wnt10a affects odontogenesis and proliferation in mesenchymal cells. Biochem Biophys Res Commun. 434:717–721. 2013. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lin F, Zhang W, Xue D, Zhu T, Li J, Chen E, Yao X and Pan Z: Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation. Int J Mol Med 37: 789-797, 2016.
APA
Lin, F., Zhang, W., Xue, D., Zhu, T., Li, J., Chen, E. ... Pan, Z. (2016). Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation. International Journal of Molecular Medicine, 37, 789-797. https://doi.org/10.3892/ijmm.2016.2479
MLA
Lin, F., Zhang, W., Xue, D., Zhu, T., Li, J., Chen, E., Yao, X., Pan, Z."Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation". International Journal of Molecular Medicine 37.3 (2016): 789-797.
Chicago
Lin, F., Zhang, W., Xue, D., Zhu, T., Li, J., Chen, E., Yao, X., Pan, Z."Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation". International Journal of Molecular Medicine 37, no. 3 (2016): 789-797. https://doi.org/10.3892/ijmm.2016.2479
Copy and paste a formatted citation
x
Spandidos Publications style
Lin F, Zhang W, Xue D, Zhu T, Li J, Chen E, Yao X and Pan Z: Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation. Int J Mol Med 37: 789-797, 2016.
APA
Lin, F., Zhang, W., Xue, D., Zhu, T., Li, J., Chen, E. ... Pan, Z. (2016). Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation. International Journal of Molecular Medicine, 37, 789-797. https://doi.org/10.3892/ijmm.2016.2479
MLA
Lin, F., Zhang, W., Xue, D., Zhu, T., Li, J., Chen, E., Yao, X., Pan, Z."Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation". International Journal of Molecular Medicine 37.3 (2016): 789-797.
Chicago
Lin, F., Zhang, W., Xue, D., Zhu, T., Li, J., Chen, E., Yao, X., Pan, Z."Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation". International Journal of Molecular Medicine 37, no. 3 (2016): 789-797. https://doi.org/10.3892/ijmm.2016.2479
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