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Article Open Access

TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway

  • Authors:
    • Gang Luo
    • Fangfei Li
    • Xiaoming Li
    • Zheng‑Guo Wang
    • Bo Zhang
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Trauma, Burns and Combined Injury, Department 4, Research Institute of Field Surgery, Third Military Medical University, Chongqing 400042, P.R. China
    Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6605-6611
    |
    Published online on: March 7, 2018
       https://doi.org/10.3892/mmr.2018.8698
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Abstract

Although tumor necrosis factor alpha (TNF‑α) is known to serve a critical role in the pathogenesis of inflammatory osteolysis, the exact mechanisms underlying the effects of TNF‑α on osteoclast recruitment and differentiation remain unclear. To investigate the mechanisms by which TNF‑α influences osteoclast differentiation, mouse bone marrow‑derived macrophages (BMMs) were used as osteoclast precursors, and osteoclastogenesis was induced by macrophage colony‑stimulating factor and receptor activator of nuclear factor (NF)‑κB ligand (RANKL) with or without TNF‑α for 4 days. Then, NF‑κB was inhibited using the inhibitor, BAY 11‑7082. The results indicated that treatment with TNF‑α alone did not induce osteoclastogenesis of BMMs. However, TNF‑α in combination with RANKL dramatically stimulated the differentiation of osteoclasts and positively regulated the expression of mRNA markers of osteoclasts. Finally, treatment of BMMs with BAY 11‑7082 prevented the formation of mature osteoclasts by BMMs treated with TNF‑α only or with RANKL, as well as the upregulation of osteoclast marker genes. Therefore, although TNF‑α does not induce osteoclastogenesis alone, it does work with RANKL to induce osteoclastic differentiation, and the NF‑κB pathway may serve an important role in this process.
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1 

Rodan GA: The development and function of the skeleton and bone metastases. Cancer. 97:726–732. 2003. View Article : Google Scholar : PubMed/NCBI

2 

Tanaka Y, Nakayamada S and Okada Y: Osteoblasts and osteoclasts in bone remodeling and inflammation. Curr Drug Targets Inflamm Allergy. 4:325–328. 2005. View Article : Google Scholar : PubMed/NCBI

3 

Pathak JL, Bravenboer N, Verschueren P, Lems WF, Luyten FP, Klein-Nulend J and Bakker AD: Inflammatory factors in the circulation of patients with active rheumatoid arthritis stimulate osteoclastogenesis via endogenous cytokine production by osteoblasts. Osteoporos Int. 25:2453–2463. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Jules J and Feng X: In vitro investigation of the roles of the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1 in murine osteoclastogenesis. Methods Mol Biol. 1155:109–123. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Córdova LA, Trichet V, Escriou V, Rosset P, Amiaud J, Battaglia S, Charrier C, Berreur M, Brion R, Gouin F, et al: Inhibition of osteolysis and increase of bone formation after local administration of siRNA-targeting RANK in a polyethylene particle-induced osteolysis model. Acta Biomater. 13:150–158. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Weitzmann MN: The Role of inflammatory cytokines, the RANKL/OPG axis, and the immunoskeletal interface in physiological bone turnover and osteoporosis. Scientifica (Cairo). 2013:1257052013.PubMed/NCBI

7 

Gallois A, Lachuer J, Yvert G, Wierinckx A, Brunet F, Rabourdin-Combe C, Delprat C, Jurdic P and Mazzorana M: Genome-wide expression analyses establish dendritic cells as a new osteoclast precursor able to generate bone-resorbing cells more efficiently than monocytes. J Bone Miner Res. 25:661–672. 2010. View Article : Google Scholar : PubMed/NCBI

8 

De Vries TJ, Schoenmaker T, Aerts D, Grevers LC, Souza PP, Nazmi K, van de Wiel M, Ylstra B, Lent PL, Leenen PJ and Everts V: M-CSF priming of osteoclast precursors can cause osteoclastogenesis-insensitivity, which can be prevented and overcome on bone. J Cell Physiol. 230:210–225. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Kim HJ, Yoon HJ, Kim SY and Yoon YR: A medium-chain fatty acid, capric acid, inhibits RANKL-induced osteoclast differentiation via the suppression of NF-kappaB signaling and blocks cytoskeletal organization and survival in mature osteoclasts. Mol Cells. 37:598–604. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Choi J, Choi SY, Lee SY, Lee JY, Kim HS, Lee SY and Lee NK: Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway. Cell Signal. 25:1222–1227. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Lampiasi N, Russo R and Zito F: The alternative faces of macrophage generate osteoclasts. Biomed Res Int. 2016:90896102016. View Article : Google Scholar : PubMed/NCBI

12 

Ishida N, Hayashi K, Hoshijima M, Ogawa T, Koga S, Miyatake Y, Kumegawa M, Kimura T and Takeya T: Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. J Biol Chem. 277:41147–41156. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Johnson RS, Spiegelman BM and Papaioannou V: Pleiotropic effects of a null mutation in the c-fos proto-oncogene. Cell. 71:577–586. 1992. View Article : Google Scholar : PubMed/NCBI

14 

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

15 

Danks L and Takayanagi H: Immunology and bone. J Biochem. 154:29–39. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Almeida M, Han L, Ambrogini E, Weinstein RS and Manolagas SC: Glucocorticoids and tumor necrosis factor α increase oxidative stress and suppress Wnt protein signaling in osteoblasts. J Biol Chem. 286:44326–44335. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Dong J, Cui X, Jiang Z and Sun J: MicroRNA-23a modulates tumor necrosis factor-alpha-induced osteoblasts apoptosis by directly targeting Fas. J Cell Biochem. 114:2738–2745. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Garcia-Lopez S, Villanueva R and Meikle MC: Alterations in the Synthesis of IL-1β, TNF-α, IL-6, and their downstream targets RANKL and OPG by mouse calvarial osteoblasts in vitro: Inhibition of bone resorption by cyclic mechanical strain. Front Endocrinol (Lausanne). 4:1602013.PubMed/NCBI

19 

Lin NY, Stefanica A and Distler JH: Autophagy: A key pathway of TNF-induced inflammatory bone loss. Autophagy. 9:1253–1255. 2013. View Article : Google Scholar : PubMed/NCBI

20 

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. View Article : Google Scholar : PubMed/NCBI

21 

Kitaura H, Kimura K, Ishida M, Kohara H, Yoshimatsu M and Takano-Yamamoto T: Immunological reaction in TNF-α-mediated osteoclast formation and bone resorption in vitro and in vivo. Clin Dev Immunol. 2013:1818492013. View Article : Google Scholar : PubMed/NCBI

22 

Mukai T, Ishida S, Ishikawa R, Yoshitaka T, Kittaka M, Gallant R, Lin YL, Rottapel R, Brotto M, Reichenberger EJ and Ueki Y: SH3BP2 cherubism mutation potentiates TNF-α -induced osteoclastogenesis via NFATc1 and TNF-α -mediated inflammatory bone loss. J Bone Miner Res. 29:2618–2635. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Osta B, Benedetti G and Miossec P: Classical and paradoxical effects of TNF-alpha on bone homeostasis. Front Immunol. 5:482014. View Article : Google Scholar : PubMed/NCBI

24 

Ritchlin CT, Haas-Smith SA, Li P, Hicks DG and Schwarz EM: Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest. 111:821–831. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Li J, Sarosi I, Yan XQ, Morony S, Capparelli C, Tan HL, McCabe S, Elliott R, Scully S, Van G, et al: RANK is the intrinsic hematopoietic cell surface receptor that controls osteoclastogenesis and regulation of bone mass and calcium metabolism. Proc Natl Acad Sci USA. 97:pp. 1566–1571. 2000; View Article : Google Scholar : PubMed/NCBI

26 

Yu Y, Yang D, Qiu L, Okamura H, Guo J and Haneji T: Tumor necrosis factor-α induces interleukin-34 expression through nuclear factor-κB activation in MC3T3-E1 osteoblastic cells. Mol Med Rep. 10:1371–1376. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Xiong J, Piemontese M, Thostenson JD, Weinstein RS, Manolagas SC and O'Brien CA: Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. Bone. 66:146–154. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Swarnkar G and Abu-Amer Y: Regulation of NF-κB signaling in osteoclasts and myeloid progenitors. Methods Mol Biol. 1280:527–542. 2015. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Luo G, Li F, Li X, Wang ZG and Zhang B: TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway. Mol Med Rep 17: 6605-6611, 2018.
APA
Luo, G., Li, F., Li, X., Wang, Z., & Zhang, B. (2018). TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway. Molecular Medicine Reports, 17, 6605-6611. https://doi.org/10.3892/mmr.2018.8698
MLA
Luo, G., Li, F., Li, X., Wang, Z., Zhang, B."TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway". Molecular Medicine Reports 17.5 (2018): 6605-6611.
Chicago
Luo, G., Li, F., Li, X., Wang, Z., Zhang, B."TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway". Molecular Medicine Reports 17, no. 5 (2018): 6605-6611. https://doi.org/10.3892/mmr.2018.8698
Copy and paste a formatted citation
x
Spandidos Publications style
Luo G, Li F, Li X, Wang ZG and Zhang B: TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway. Mol Med Rep 17: 6605-6611, 2018.
APA
Luo, G., Li, F., Li, X., Wang, Z., & Zhang, B. (2018). TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway. Molecular Medicine Reports, 17, 6605-6611. https://doi.org/10.3892/mmr.2018.8698
MLA
Luo, G., Li, F., Li, X., Wang, Z., Zhang, B."TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway". Molecular Medicine Reports 17.5 (2018): 6605-6611.
Chicago
Luo, G., Li, F., Li, X., Wang, Z., Zhang, B."TNF‑α and RANKL promote osteoclastogenesis by upregulating RANK via the NF‑κB pathway". Molecular Medicine Reports 17, no. 5 (2018): 6605-6611. https://doi.org/10.3892/mmr.2018.8698
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