Mycobacterium tuberculosis infection increases the number of osteoclasts and inhibits osteoclast apoptosis by regulating TNF‑α‑mediated osteoclast autophagy

Liu,Wei; Zhou,Juan; Niu,Fei; Pu,Feifei; Wang,Zhiwei; Huang,Mi; Zhao,Xiaolong; Yang,Lin; Tao,Pengfei; Xia ,Ping; Feng,Jing

doi:10.3892/etm.2020.8903

Mycobacterium tuberculosis infection increases the number of osteoclasts and inhibits osteoclast apoptosis by regulating TNF‑α‑mediated osteoclast autophagy

Authors:
- Wei Liu
- Juan Zhou
- Fei Niu
- Feifei Pu
- Zhiwei Wang
- Mi Huang
- Xiaolong Zhao
- Lin Yang
- Pengfei Tao
- Ping Xia
- Jing Feng
View Affiliations

Affiliations: Department of Orthopaedics, First Hospital of Wuhan, Wuhan, Hubei 430022, P.R. China
Published online on: June 18, 2020 https://doi.org/10.3892/etm.2020.8903
Pages: 1889-1898
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Osteoarticular tuberculosis, a chronic inflammatory disease characterized by Mycobacterium tuberculosis (M.tb) infection, has become a serious problem in China. The present study was conducted to determine the mechanism of action of tumor necrosis factor (TNF)‑α in the pathogenesis of osteoarticular tuberculosis. The number of osteoclasts in osteoarticular tuberculosis tissue samples was detected by tartrate‑resistant acid phosphatase staining. Autophagy and apoptosis of osteoclasts were detected by western blotting, reverse transcription‑quantitative PCR, transmission electron microscopy and TUNEL staining. The results showed that autophagy and the number of osteoclasts increased in the lesions of patients with osteoarticular tuberculosis compared with osteoarthritis samples. Moreover, activation of osteoclast autophagy inhibited the apoptosis of osteoclasts infected with M.tb, and increased the expression level of TNF‑α. The results showed that TNF‑α enhanced the autophagic activity of M.tb‑infected osteoclasts and inhibited cell apoptosis. These findings indicated that M.tb infection induced osteoclast production and inhibited osteoclast apoptosis by regulating TNF‑α‑mediated osteoclast autophagy, revealing a new mechanism for TNF‑α in the pathogenesis of osteoarticular tuberculosis.

View Figures

View References

1	Tiwari U, Ramachandran VG, Das S and Kumar S: Interleukin-3 and interleukin-17 do not play a dynamic role in the immunopathogenesis of osteoarticular tuberculosis. Indian J Tuberc. 61:142–147. 2014.PubMed/NCBI
2	Kaufmann SH, Lange C, Rao M, Balaji KN, Lotze M, Schito M, Zumla AI and Maeurer M: Progress in tuberculosis vaccine development and host-directed therapies-a state of the art review. Lancet Respir Med. 2:301–320. 2014.PubMed/NCBI View Article : Google Scholar
3	Agarwal A: Acute suppurative presentation of osteoarticular tuberculosis in children. Indian J Tuberc. 58:66–71. 2011.PubMed/NCBI
4	Hu P, Zhang H, Fleming J, Zhu G, Zhang S, Wang Y, Liu F, Yi S, Chen Z, Chen Z, et al: Retrospective analysis of false-positive and disputed rifampin resistance Xpert MTB/RIF assay results in clinical samples from a referral hospital in hunan, China. J Clin Microbiol. 57: pii:e01707–e01718. 2019.PubMed/NCBI View Article : Google Scholar
5	Wu W, Lyu J, Cheng P, Cheng Y, Zhang Z, Li L, Zheng Y and Xu J: Improvement in clinical outcome and infection control using molecular diagnostic techniques for early detection of MDR tuberculous spondylitis: A multicenter retrospective study. Emerg Microbes Infect. 6(e97)2017.PubMed/NCBI View Article : Google Scholar
6	Trébucq A, Decroo T, Van Deun A, Piubello A, Chiang CY, Koura KG and Schwoebel V: Short-course regimen for multidrug-resistant tuberculosis: A decade of evidence. J Clin Med. 9: pii(E55)2019.PubMed/NCBI View Article : Google Scholar
7	Zhou Y, Tan CY, Mo ZJ, Gao QL, He D, Li J, Huang RF, Li YB, Guo CF, Guo Q, et al: Polymorphisms in the SP110 and TNF-α gene and susceptibility to pulmonary and spinal tuberculosis among southern chinese population. Dis Markers. 2017(4590235)2017.PubMed/NCBI View Article : Google Scholar
8	Meghji S, White PA, Nair SP, Reddi K, Heron K, Henderson B, Zaliani A, Fossati G, Mascagni P, Hunt JF, et al: Mycobacterium tuberculosis chaperonin 10 stimulates bone resorption: A potential contributory factor in Pott's disease. J Exp Med. 186:1241–1246. 1997.PubMed/NCBI View Article : Google Scholar
9	Liu X, Jia W, Wang H, Wang Y, Ma J, Wang H, Zhou X and Li G: Establishment of a rabbit model of spinal tuberculosis using Mycobacterium tuberculosis strain H37Rv. Jpn J Infect Dis. 68:89–97. 2015.PubMed/NCBI View Article : Google Scholar
10	Lawlor C, O'Connor G, O'Leary S, Gallagher PJ, Cryan SA, Keane J and O'Sullivan MP: Treatment of Mycobacterium tuberculosis-infected macrophages with Poly(Lactic-Co-Glycolic Acid) microparticles drives NFκB and autophagy dependent bacillary killing. PLoS One. 11(e0149167)2016.PubMed/NCBI View Article : Google Scholar
11	Tateosian NL, Pellegrini JM, Amiano NO, Rolandelli A, Casco N, Palmero DJ, Colombo MI and García VE: IL17A augments autophagy in Mycobacterium tuberculosis-infected monocytes from patients with active tuberculosis in association with the severity of the disease. Autophagy. 13:1191–1204. 2017.PubMed/NCBI View Article : Google Scholar
12	Ozeki N, Mogi M, Hase N, Hiyama T, Yamaguchi H, Kawai R, Matsumoto T and Nakata K: Bone morphogenetic protein-induced cell differentiation involves Atg7 and Wnt16 sequentially in human stem cell-derived osteoblastic cells. Exp Cell Res. 347:24–41. 2016.PubMed/NCBI View Article : Google Scholar
13	Lin NY, Beyer C, Giessl A, Kireva T, Scholtysek C, Uderhardt S, Munoz LE, Dees C, Distler A, Wirtz S, et al: Autophagy regulates TNFα-mediated joint destruction in experimental arthritis. Ann Rheum Dis. 72:761–768. 2013.PubMed/NCBI View Article : Google Scholar
14	Espert L, Beaumelle B and Vergne I: Autophagy in Mycobacterium tuberculosis and HIV infections. Front Cell Infect Microbio. 5(49)2015.PubMed/NCBI View Article : Google Scholar
15	Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI and Deretic V: Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell. 119:753–766. 2004.PubMed/NCBI View Article : Google Scholar
16	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
17	Aydin V, Akici A, Isli F, Aksoy M, Aydin M and Gursoz H: Relative risk of tuberculosis in patients with rheumatic diseases managed with anti-tumour necrosis factor-alpha therapy: A nationwide cohort study. J Clin Pharm The. 44:553–560. 2019.PubMed/NCBI View Article : Google Scholar
18	Guo C, Wang L, Zhao Y, Jiang B, Luo J and Shi D: BOS-93, a novel bromophenol derivative, induces apoptosis and autophagy in human A549 lung cancer cells via PI3K/Akt/mTOR and MAPK signaling pathway. Exp Ther Med. 17:3848–3858. 2019.PubMed/NCBI View Article : Google Scholar
19	Arai A, Kim S, Goldshteyn V, Kim T, Park NH, Wang CY and Kim RH: Beclin1 modulates bone homeostasis by regulating osteoclast and chondrocyte differentiation. J Bone Miner Res. 34:1753–1766. 2019.PubMed/NCBI View Article : Google Scholar
20	Sabir N, Hussain T, Liao Y, Wang J, Song Y, Shahid M, Cheng G, Mangi MH, Yao J, Yang L, et al: Kallikrein 12 regulates innate resistance of murine macrophages against Mycobacterium bovis infection by modulating autophagy and apoptosis. Cells. 8: pii(E415)2019.PubMed/NCBI View Article : Google Scholar
21	Trejo-Solís C, Serrano-Garcia N, Escamilla-Ramírez Á, Castillo-Rodríguez RA, Jimenez-Farfan D, Palencia G, Calvillo M, Alvarez-Lemus MA, Flores-Nájera A, Cruz-Salgado A and Sotelo J: Autophagic and Apoptotic pathways as targets for chemotherapy in glioblastoma. Int J Mol Sci. 19: pii(E3773)2018.PubMed/NCBI View Article : Google Scholar
22	Park YE, Musson DS, Naot D and Cornish J: Cell-cell communication in bone development and whole-body homeostasis and pharmacological avenues for bone disorders. Curr Opin Pharmacol. 34:21–35. 2017.PubMed/NCBI View Article : Google Scholar
23	Hoshino A, Hanada S, Yamada H, Mii S, Takahashi M, Mitarai S, Yamamoto K and Manome Y: Mycobacterium tuberculosis escapes from the phagosomes of infected human osteoclasts reprograms osteoclast development via dysregulation of cytokines and chemokines. Pathog Dis. 70:28–39. 2014.PubMed/NCBI View Article : Google Scholar
24	Yi L, Li Z, Jiang H, Cao Z, Liu J and Zhang X: Gene modification of transforming growth factor β (TGF-β) and interleukin 10 (IL-10) in suppressing Mt sonicate induced osteoclast formation and bone absorption. Med Sci Monit. 24:5200–5207. 2018.PubMed/NCBI View Article : Google Scholar
25	Sun KT, Chen MY, Tu MG, Wang IK, Chang SS and Li CY: MicroRNA-20a regulates autophagy related protein-ATG16L1 in hypoxia-induced osteoclast differentiation. Bone. 73:145–153. 2015.PubMed/NCBI View Article : Google Scholar
26	DeSelm CJ, Miller BC, Zou W, Beatty WL, van Meel E, Takahata Y, Klumperman J, Tooze SA, Teitelbaum SL and Virgin HW: Autophagy proteins regulate the secretory component of osteoclastic bone resorption. Dev Cell. 21:966–974. 2011.PubMed/NCBI View Article : Google Scholar
27	Xing L, Xiu Y and Boyce BF: Osteoclast fusion and regulation by RANKL-dependent and independent factors. World J Orthop. 3:212–222. 2012.PubMed/NCBI View Article : Google Scholar
28	Mootoo A, Stylianou E, Arias MA and Reljic R: TNF-alpha in tuberculosis: A cytokine with a split personality. Inflamm Allergy Drug Targets. 8:53–62. 2009.PubMed/NCBI View Article : Google Scholar
29	Chen H, Cheng C, Li M, Gao S, Li S and Sun H: Expression of TNF-α, IFN-γ, TGF-β and IL-4 in the spinal tuberculous focus and its impact on the disease. Cell Biochem Biophys. 70:1759–1764. 2014.PubMed/NCBI View Article : Google Scholar
30	Patil T, Garg RK, Jain A, Goel MM, Malhotra HS, Verma R, Singh GP and Sharma PK: Serum and CSF cytokines and matrix metalloproteinases in spinal tuberculosis. Inflamm Res. 64:97–106. 2015.PubMed/NCBI View Article : Google Scholar
31	Mattos AM, Almeida Cde S, Franken KL, Alves CC, Abramo C, de Souza MA, L'Hotellier M, Alves MJ, Ferreira AP, Oliveira SC, et al: Increased IgG1, IFN-gamma, TNF-alpha and IL-6 responses to Mycobacterium tuberculosis antigens in patients with tuberculosis are lower after chemotherapy. Int Immunol. 22:775–782. 2010.PubMed/NCBI View Article : Google Scholar
32	Zheng M, Shi S, Wei W, Zheng Q, Wang Y, Ying X and Lu D: Correlation between MBL2/CD14/TNF-α gene polymorphisms and susceptibility to spinal tuberculosis in Chinese population. Biosci Rep. 38: pii(BSR20171140)2018.PubMed/NCBI View Article : Google Scholar
33	Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, et al: Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 191:275–286. 2000.PubMed/NCBI View Article : Google Scholar
34	Osta B, Benedetti G and Miossec P: Classical and paradoxical effects of TNF-α on bone homeostasis. Front Immunol. 5(48)2014.PubMed/NCBI View Article : Google Scholar
35	Kawai VK, Stein CM, Perrien DS and Griffin MR: Effects of anti-tumor necrosis factor α agents on bone. Curr Opin Rheumatol. 24:576–585. 2012.PubMed/NCBI View Article : Google Scholar
36	Lin NY, Stefanica A and Distler JH: Autophagy: A key pathway of TNF-induced inflammatory bone loss. Autophagy. 9:1253–1255. 2013.PubMed/NCBI View Article : Google Scholar
37	Tong X, Gu J, Song R, Wang D, Sun Z, Sui C, Zhang C, Liu X, Bian J and Liu Z: Osteoprotegerin inhibit osteoclast differentiation and bone resorption by enhancing autophagy via AMPK/mTOR/p70S6K signaling pathway in vitro. J Cell Biochem. 2018, doi: 10.1002/jcb.27468. [Epub ahead of print].