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
June-2018 Volume 17 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-2018 Volume 17 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

Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways

  • Authors:
    • Liping Shi
    • Suping Zhao
    • Qian Chen
    • Youwei Wu
    • Jian Zhang
    • Na Li
  • View Affiliations / Copyright

    Affiliations: Department II of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
  • Pages: 7947-7951
    |
    Published online on: March 29, 2018
       https://doi.org/10.3892/mmr.2018.8835
  • 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

Receptor activator of nuclear factor‑κB ligand (RANKL), a member of the tumor necrosis factor receptor-ligand family, is a crucial factor involved in osteoclast differentiation. Crocin, a pharmacologically active component of Crocus sativus L., has been reported to attenuate ovariectomy‑induced osteoporosis in rats. However, the molecular mechanism underlying the effect of crocin on osteoclast formation remains to be determined. The present study aimed to investigate the effect of crocin on RANKL‑induced osteoclastogenesis and its underlying molecular mechanism. Results demonstrated that crocin decreased osteoclastogenesis in bone marrow‑derived macrophages (BMMs). In addition, the expression levels of osteoclast marker proteins were downregulated by crocin. Mechanistically, crocin inhibited RANKL‑induced activation of nuclear factor‑κB (NF‑κB) by suppressing inhibitor of κBα degradation and preventing NF‑κB p65 subunit nuclear translocation, and by activating c‑Jun N‑terminal kinase (JNK) in BMMs. In summary, the results of the present study suggested that crocin downregulates osteoclast differentiation via inhibition of JNK and NF‑κB signaling pathways. Thus, crocin may be a potential therapeutic agent for the treatment of osteoclast‑associated diseases, including osteoporosis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Hennemann A: Osteoporosis: Prevention, diagnosis and therapy. Med Monatsschr Pharm. 25:164–167. 2002.(In German). PubMed/NCBI

2 

Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A and Tosteson A: Incidence and economic burden of osteoporosis-related fractures in the United States, 2005–2025. J Bone Miner Res. 22:465–475. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Boyle WJ, Simonet WS and Lacey DL: Osteoclast differentiation and activation. Nature. 423:337–342. 2003. View Article : Google Scholar : PubMed/NCBI

4 

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

5 

Karst M, Gorny G, Galvin RJ and Oursler MJ: Roles of stromal cell RANKL, OPG, and M-CSF expression in biphasic TGF-beta regulation of osteoclast differentiation. J Cell Physiol. 200:99–106. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Roodman GD: Regulation of osteoclast differentiation. Ann N Y Acad Sci. 1068:100–109. 2006. View Article : Google Scholar : PubMed/NCBI

7 

Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, et al: Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA. 95:3597–3602. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Takayanagi H, Iizuka H, Juji T, Nakagawa T, Yamamoto A, Miyazaki T, Koshihara Y, Oda H, Nakamura K and Tanaka S: Involvement of receptor activator of nuclear factor kappaB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum. 43:259–269. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Asagiri M and Takayanagi H: The molecular understanding of osteoclast differentiation. Bone. 40:251–264. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Hemshekhar M, Santhosh Sebastin M, Sunitha K, Thushara RM, Kemparaju K, Rangappa KS and Girish KS: A dietary colorant crocin mitigates arthritis and associated secondary complications by modulating cartilage deteriorating enzymes, inflammatory mediators and antioxidant status. Biochimie. 94:2723–2733. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Li K, Li Y, Ma Z and Zhao J: Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK. Int J Mol Med. 36:1291–1299. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Thushara RM, Hemshekhar M, Santhosh MS, Jnaneshwari S, Nayaka SC, Naveen S, Kemparaju K and Girish KS: Crocin, a dietary additive protects platelets from oxidative stress-induced apoptosis and inhibits platelet aggregation. Mol Cell Biochem. 373:73–83. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Aung HH, Wang CZ, Ni M, Fishbein A, Mehendale SR, Xie JT, Shoyama CY and Yuan CS: Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol. 29:175–180. 2007.PubMed/NCBI

14 

Ding Q, Zhong H, Qi Y, Cheng Y, Li W, Yan S and Wang X: Anti-arthritic effects of crocin in interleukin-1β-treated articular chondrocytes and cartilage in a rabbit osteoarthritic model. Inflamm Res. 62:17–25. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Cao PC, Xiao WX, Yan YB, Zhao X, Liu S, Feng J, Zhang W, Wang J, Feng YF and Lei W: Preventive effect of crocin on osteoporosis in an ovariectomized rat model. Evid Based Complement Alternat Med. 2014:8251812014. View Article : Google Scholar : PubMed/NCBI

16 

Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT and Martin TJ: Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev. 20:345–357. 1999. View Article : Google Scholar : PubMed/NCBI

17 

Tanaka S, Nakamura K, Takahasi N and Suda T: Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system. Immunol Rev. 208:30–49. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue JI, et al: Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Deve Cell. 3:889–901. 2002. View Article : Google Scholar

19 

Arai A, Mizoguchi T, Harada S, Kobayashi Y, Nakamichi Y, Yasuda H, Penninger JM, Yamada K, Udagawa N and Takahashi N: Fos plays an essential role in the upregulation of RANK expression in osteoclast precursors within the bone microenvironment. J Cell Sci. 125:2910–2917. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Kobayashi N, Kadono Y, Naito A, Matsumoto K, Yamamoto T, Tanaka S and Inoue J: Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO J. 20:1271–1280. 2001. View Article : Google Scholar : PubMed/NCBI

21 

Grigoriadis AE, Wang ZQ, Cecchini MG, Hofstetter W, Felix R, Fleisch HA and Wagner EF: c-Fos: A key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science. 266:443–448. 1994. View Article : Google Scholar : PubMed/NCBI

22 

Huh JE, Lee WI, Kang JW, Nam D, Choi DY, Park DS, Lee SH and Lee JD: Formononetin attunuates osteoclastogenesis via suppressing the RANKL-induced activation of NF-κB, c-Fos, and nuclear factor of activated T-cells cytoplasmic 1 signaling pathway. J Nat Prod. 77:2423–2431. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Ikeda F, Nishimura R, Matsubara T, Tanaka S, Inoue J, Reddy SV, Hata K, Yamashita K, Hiraga T, Watanabe T, et al: Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation. J Clin Invest. 114:475–484. 2004. View Article : Google Scholar : PubMed/NCBI

24 

Miyazaki T, Katagiri H, Kanegae Y, Takayanagi H, Sawada Y, Yamamoto A, Pando MP, Asano T, Verma IM, Oda H, et al: Reciprocal role of ERK and NF-kappaB pathways in survival and activation of osteoclasts. J Cell Biol. 148:333–342. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Lee ZH and Kim HH: Signal transduction by receptor activator of nuclear factor kappa B in osteoclasts. Biochem Biophys Res Commun. 305:211–214. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Yamashita T, Yao Z, Li F, Zhang Q, Badell IR, Schwarz EM, Takeshita S, Wagner EF, Noda M, Matsuo K, et al: NF-kappaB p50 and p52 regulate receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1. J Biol Chem. 282:18245–18253. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Novack DV, Yin L, Hagen-Stapleton A, Schreiber RD, Goeddel DV, Ross FP and Teitelbaum SL: The IkappaB function of NF-kappaB2 p100 controls stimulated osteoclastogenesis. J Exp Med. 198:771–781. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Chaisson ML, Branstetter DG, Derry JM, Armstrong AP, Tometsko ME, Takeda K, Akira S and Dougall WC: Osteoclast differentiation is impaired in the absence of inhibitor of kappaB kinase alpha. J Biol Chem. 279:54841–54848. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Zou W, Amcheslavsky A, Takeshita S, Drissi H and Bar-Shavit Z: TNF-alpha expression is transcriptionally regulated by RANK ligand. J Cell Physiol. 202:371–378. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Shi L, Zhao S, Chen Q, Wu Y, Zhang J and Li N: Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways. Mol Med Rep 17: 7947-7951, 2018.
APA
Shi, L., Zhao, S., Chen, Q., Wu, Y., Zhang, J., & Li, N. (2018). Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways. Molecular Medicine Reports, 17, 7947-7951. https://doi.org/10.3892/mmr.2018.8835
MLA
Shi, L., Zhao, S., Chen, Q., Wu, Y., Zhang, J., Li, N."Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways". Molecular Medicine Reports 17.6 (2018): 7947-7951.
Chicago
Shi, L., Zhao, S., Chen, Q., Wu, Y., Zhang, J., Li, N."Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways". Molecular Medicine Reports 17, no. 6 (2018): 7947-7951. https://doi.org/10.3892/mmr.2018.8835
Copy and paste a formatted citation
x
Spandidos Publications style
Shi L, Zhao S, Chen Q, Wu Y, Zhang J and Li N: Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways. Mol Med Rep 17: 7947-7951, 2018.
APA
Shi, L., Zhao, S., Chen, Q., Wu, Y., Zhang, J., & Li, N. (2018). Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways. Molecular Medicine Reports, 17, 7947-7951. https://doi.org/10.3892/mmr.2018.8835
MLA
Shi, L., Zhao, S., Chen, Q., Wu, Y., Zhang, J., Li, N."Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways". Molecular Medicine Reports 17.6 (2018): 7947-7951.
Chicago
Shi, L., Zhao, S., Chen, Q., Wu, Y., Zhang, J., Li, N."Crocin inhibits RANKL‑induced osteoclastogenesis by regulating JNK and NF‑κB signaling pathways". Molecular Medicine Reports 17, no. 6 (2018): 7947-7951. https://doi.org/10.3892/mmr.2018.8835
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