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
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
June-2024 Volume 27 Issue 6

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
June-2024 Volume 27 Issue 6

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

S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling

  • Authors:
    • Jing Xin
    • Zhaoxu Wang
    • Yanju Shen
    • Jing Bai
    • Yafei Shen
  • View Affiliations / Copyright

    Affiliations: Department of Endocrinology and Diabetes, Luohe Central Hospital, Luohe First People's Hospital, The First Affiliated Hospital of Luohe Medical College, Luohe, Henan 462000, P.R. China
    Copyright: © Xin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 250
    |
    Published online on: April 15, 2024
       https://doi.org/10.3892/etm.2024.12538
  • 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

Osteogenesis is a complex process of bone formation regulated by various factors, yet its underlying molecular mechanisms remain incompletely understood. The present study aimed to investigate the role of S100A16, a novel member of the S100 protein family, in the osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) and uncover a novel Smad4‑mitogen‑activated protein kinase (MAPK)/Jun N‑terminal kinase (JNK) signaling axis. In the present study, the expression level of S100A16 in bone tissues and BMSCs from ovariectomized rats was evaluated and then the impact of S100A16 silencing on osteogenic differentiation was examined. Increased S100A16 expression was observed in bone tissues and BMSCs from ovariectomized rats, and S100A16 silencing promoted osteogenic differentiation. Further transcriptomic sequencing revealed that the Smad4 pathway was involved in S100A16 silencing‑induced osteogenesis. The results of western blot analysis revealed that S100A16 overexpression not only downregulated Smad4 but also activated MAPK/JNK signaling, which was validated by treatment with MAPK and JNK inhibitors U0126 and SP600125. Overall, in the present study, the novel regulatory factors influencing osteogenic differentiation were elucidated and mechanistic insights that could aid in the development of targeted therapeutic strategies for patients with osteoporosis were provided.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Fedarko NS: Osteoblast/osteoclast development and function in osteogenesis imperfecta. Osteogenesis Imperfecta. Academic Press, pp45-56, 2014.

2 

Kim JM, Lin C, Stavre Z, Greenblatt MB and Shim JH: Osteoblast-osteoclast communication and bone homeostasis. Cells. 9(2073)2020.PubMed/NCBI View Article : Google Scholar

3 

Zhang J, Zhang X, Zhang L, Zhou F, van Dinther M and Ten Dijke P: LRP8 mediates Wnt/β-catenin signaling and controls osteoblast differentiation. J Bone Miner Res. 27:2065–2074. 2012.PubMed/NCBI View Article : Google Scholar

4 

Day TF, Guo X, Garrett-Beal L and Yang Y: Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell. 8:739–750. 2005.PubMed/NCBI View Article : Google Scholar

5 

Yamaguchi A, Komori T and Suda T: Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr Rev. 21:393–411. 2000.PubMed/NCBI View Article : Google Scholar

6 

Skillington J, Choy L and Derynck R: Bone morphogenetic protein and retinoic acid signaling cooperate to induce osteoblast differentiation of preadipocytes. J Cell Biol. 159:135–146. 2002.PubMed/NCBI View Article : Google Scholar

7 

Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS and Lian JB: Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem. 280:33132–33140. 2005.PubMed/NCBI View Article : Google Scholar

8 

Yang W, Li HY, Wu YF, Mi RJ, Liu WZ, Shen X, Lu YX, Jiang YH, Ma MJ and Shen HY: ac4C acetylation of RUNX2 catalyzed by NAT10 spurs osteogenesis of BMSCs and prevents ovariectomy-induced bone loss. Mol Ther Nucleic Acids. 26:135–147. 2021.PubMed/NCBI View Article : Google Scholar

9 

Zhang B, Zhang X, Xiao J, Zhou X, Chen Y and Gao C: Neuropeptide Y upregulates Runx2 and osterix and enhances osteogenesis in mouse MC3T3-E1 cells via an autocrine mechanism. Mol Med Rep. 22:4376–4382. 2020.PubMed/NCBI View Article : Google Scholar

10 

Lee KM, Park KH, Hwang JS, Lee M, Yoon DS, Ryu HA, Jung HS, Park KW, Kim J, Park SW, et al: Inhibition of STAT5A promotes osteogenesis by DLX5 regulation. Cell Death Dis. 9(1136)2018.PubMed/NCBI View Article : Google Scholar

11 

Li D, Zhang R, Zhu W, Xue Y, Zhang Y, Huang Q, Liu M and Liu Y: S100A16 inhibits osteogenesis but stimulates adipogenesis. Mol Biol Rep. 40:3465–3473. 2013.PubMed/NCBI View Article : Google Scholar

12 

Sturchler E, Cox JA, Durussel I, Weibel M and Heizmann CW: S100A16, a novel calcium-binding protein of the EF-hand superfamily. J Biol Chem. 281:38905–38917. 2006.PubMed/NCBI View Article : Google Scholar

13 

Liu DD, Zhang JC, Zhang Q, Wang SX and Yang MS: TGF-β/BMP signaling pathway is involved in cerium-promoted osteogenic differentiation of mesenchymal stem cells. J Cell Biochem. 114:1105–1114. 2013.PubMed/NCBI View Article : Google Scholar

14 

Zhang LT, Liu RM, Luo Y, Zhao YJ, Chen DX, Yu CY and Xiao JH: Hyaluronic acid promotes osteogenic differentiation of human amniotic mesenchymal stem cells via the TGF-β/Smad signalling pathway. Life Sci. 232(116669)2019.PubMed/NCBI View Article : Google Scholar

15 

Zhao M, Mishra L and Deng CX: The role of TGF-β/SMAD4 signaling in cancer. Int J Biol Sci. 14:111–123. 2018.PubMed/NCBI View Article : Google Scholar

16 

Cai H, Yang X, Jiang Z, Liang B, Cai Q and Huang H: Upregulation of SMAD4 inhibits thyroid cancer cell growth via MAPK/JNK pathway repression. Trop J Pharm Res. 18:2473–2478. 2019.

17 

Wang P, Wang Y, Tang W, Wang X, Pang Y, Yang S, Wei Y, Gao H, Wang D and Cao Z: Bone morphogenetic protein-9 enhances osteogenic differentiation of human periodontal ligament stem cells via the JNK pathway. PLoS One. 12(e0169123)2017.PubMed/NCBI View Article : Google Scholar

18 

Zhu WQ, Ming PP, Zhang SM and Qiu J: Role of MAPK/JNK signaling pathway on the regulation of biological behaviors of MC3T3-E1 osteoblasts under titanium ion exposure. Mol Med Rep. 22:4792–4800. 2020.PubMed/NCBI View Article : Google Scholar

19 

Lei Z, Xiaoying Z and Xingguo L: Ovariectomy-associated changes in bone mineral density and bone marrow haematopoiesis in rats. Int J Exp Pathol. 90:512–519. 2009.PubMed/NCBI View Article : Google Scholar

20 

Du D, Zhou Z, Zhu L, Hu X, Lu J, Shi C, Chen F and Chen A: TNF-α suppresses osteogenic differentiation of MSCs by accelerating P2Y2 receptor in estrogen-deficiency induced osteoporosis. Bone. 117:161–170. 2018.PubMed/NCBI View Article : Google Scholar

21 

Chen W, Chen X, Chen AC, Shi Q, Pan G, Pei M, Yang H, Liu T and He F: Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells by preserving SIRT1-mediated intracellular antioxidant properties. Free Radic Biol Med. 146:92–106. 2020.PubMed/NCBI View Article : Google Scholar

22 

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

23 

Song B, Estrada KD and Lyons KM: Smad signaling in skeletal development and regeneration. Cytokine Growth Factor Rev. 20:379–388. 2009.PubMed/NCBI View Article : Google Scholar

24 

Park JS, Kim M, Song NJ, Kim JH, Seo D, Lee JH, Jung SM, Lee JY, Lee J, Lee YS, et al: A reciprocal role of the Smad4-Taz axis in osteogenesis and adipogenesis of mesenchymal stem cells. Stem Cells. 37:368–381. 2019.PubMed/NCBI View Article : Google Scholar

25 

Pakravan K, Razmara E, Mahmud Hussen B, Sattarikia F, Sadeghizadeh M and Babashah S: SMAD4 contributes to chondrocyte and osteocyte development. J Cell Mol Med. 26:1–15. 2022.PubMed/NCBI View Article : Google Scholar

26 

Gu H, Huang Z, Yin X, Zhang J, Gong L, Chen J, Rong K, Xu J, Lu L and Cui L: Role of c-Jun N-terminal kinase in the osteogenic and adipogenic differentiation of human adipose-derived mesenchymal stem cells. Exp Cell Res. 339:112–121. 2015.PubMed/NCBI View Article : Google Scholar

27 

Li Y, Wagner ER, Yan Z, Wang Z, Luther G, Jiang W, Ye J, Wei Q, Wang J, Zhao L, et al: The calcium-binding protein S100A6 accelerates human osteosarcoma growth by promoting cell proliferation and inhibiting osteogenic differentiation. Cell Physiol Biochem. 37:2375–2392. 2015.PubMed/NCBI View Article : Google Scholar

28 

Su Y, Qi R, Li L, Wang X, Li S, Zhao X, Hou R, Ma W, Liu D, Zheng J and Shi M: An immune-related gene prognostic risk index for pancreatic adenocarcinoma. Front Immunol. 13(945878)2022.PubMed/NCBI View Article : Google Scholar

29 

Wang R, Wu Y, Yu J, Yang G, Yi H and Xu B: Plasma messenger RNAs identified through bioinformatics analysis are novel, non-invasive prostate cancer biomarkers. Onco Targets Ther. 13:541–548. 2020.PubMed/NCBI View Article : Google Scholar

30 

Leclerc E and Vetter SW: The role of S100 proteins and their receptor RAGE in pancreatic cancer. Biochim Biophys Acta. 1852:2706–2711. 2015.PubMed/NCBI View Article : Google Scholar

31 

Zhang X, Cao J, Pei Y, Zhang J and Wang Q: Smad4 inhibits cell migration via suppression of JNK activity in human pancreatic carcinoma PANC-1 cells. Oncol Lett. 11:3465–3470. 2016.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xin J, Wang Z, Shen Y, Bai J and Shen Y: S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling. Exp Ther Med 27: 250, 2024.
APA
Xin, J., Wang, Z., Shen, Y., Bai, J., & Shen, Y. (2024). S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling. Experimental and Therapeutic Medicine, 27, 250. https://doi.org/10.3892/etm.2024.12538
MLA
Xin, J., Wang, Z., Shen, Y., Bai, J., Shen, Y."S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling". Experimental and Therapeutic Medicine 27.6 (2024): 250.
Chicago
Xin, J., Wang, Z., Shen, Y., Bai, J., Shen, Y."S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling". Experimental and Therapeutic Medicine 27, no. 6 (2024): 250. https://doi.org/10.3892/etm.2024.12538
Copy and paste a formatted citation
x
Spandidos Publications style
Xin J, Wang Z, Shen Y, Bai J and Shen Y: S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling. Exp Ther Med 27: 250, 2024.
APA
Xin, J., Wang, Z., Shen, Y., Bai, J., & Shen, Y. (2024). S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling. Experimental and Therapeutic Medicine, 27, 250. https://doi.org/10.3892/etm.2024.12538
MLA
Xin, J., Wang, Z., Shen, Y., Bai, J., Shen, Y."S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling". Experimental and Therapeutic Medicine 27.6 (2024): 250.
Chicago
Xin, J., Wang, Z., Shen, Y., Bai, J., Shen, Y."S100 calcium‑binding protein A16 suppresses the osteogenic differentiation of rat bone marrow mesenchymal stem cells by inhibiting SMAD family member 4 signaling". Experimental and Therapeutic Medicine 27, no. 6 (2024): 250. https://doi.org/10.3892/etm.2024.12538
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