Tumor necrosis factor alpha enhances the bone-resorptive capabilities of osteoclasts by improving the expression and activity of vocuolar-type ATPase

doi:10.3969/j.issn.2095-4344.2014.38.010

Abstract

Abstract:

BACKGROUND: Vocuolar-type ATPase (V-ATPase) is highly expressed in osteoclasts and especially plays an important role in osteoclastic bone resorption. Tumor necrosis factor-α is a potent stimulator of bone resorption. However, the effect of tumor necrosis factor-α on expression and activity of V-ATPase is still not clear.
OBJECTIVE: To investigate the mechanism of tumor necrosis factor-α to promote osteoclastic bone resorption by observing expression and activity of V-ATPase.
METHODS: Osteoclasts cultured in vitro were intervened by different concentrations of tumor necrosis factor-α (5, 10, 30 μg/L) in order to observe the changes in expression and enzyme activity of V-ATPase and its effects on bone resorption of osteoclasts. Under an inverted microscope, we observed the formation of resorption lacunas, and bone resorption area was analyzed using Image J software.
RESULTS AND CONCLUSION: The expression and activity of V-ATPase increased significantly after 48 hours of tumor necrosis factor-α intervention and the increase of tumor necrosis factor-α concentration might enhance this effect. In addition, osteoclastic bone resorption was promoted after intervention with tumor necrosis factor-α. The bone-resorbing capabilities of osteoclasts increased in parallel with the concentration of tumor necrosis
factor-α.The results suggested that tumor necrosis factor-α, as a significant inflammatory mediator involved in the pathological process of bone resorption, not only promotes formation of osteoclasts but also enhances bone-resorbing capabilities of osteoclasts by increasing V-ATPase expression and activity.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: tumor necrosis factor-alpha, osteoclasts, adenosine triphosphatases

CLC Number:

R318

Zhu Wei-ping, Lin Lin, Liu Geng-rong, Li Zhong-he, Liu Shuang-xin, Shi Wei. Tumor necrosis factor alpha enhances the bone-resorptive capabilities of osteoclasts by improving the expression and activity of vocuolar-type ATPase[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(38): 6123-6128.

Figures/Tables 3

References

[1] Sims NA, Gooi JH. Bone remodeling: Multiple cellular interactions required for coupling of bone formation and resorption.Semin Cell Dev Biol.2008;19(5):444-451.
[2] Sims NA, Vrahnas C.Regulation of cortical and trabecular bone mass by communication between osteoblasts, osteocytes and osteoclasts. Arch Biochem Biophys. 2014 May 26. pii: S0003-9861(14)00172-176.
[3] Parfitt AM. Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone.J Cell Biochem.1994;55(3):273-286.
[4] Udagawa N, Takahashi N, Akatsu T, et al. Origin of osteoclasts: mature monocytes and macrophages are capable of differentiating into osteoclasts under a suitable microenvironment prepared by bone marrow-derived stromal cells. Proc Natl Acad Sci U S A.1990;87(18):7260-7264.
[5] 朱伟平;史伟;林琳;等.核因子κB受体活化因子配体诱导破骨细胞前体的培养与分化[J].中国组织工程研究,2013,17(46): 7981-7987.
[6] 刘波,于世凤,庞淑珍.新伐他汀体外对破骨细胞性骨吸收及大鼠骨代谢的影响[J].中国骨质疏松杂志,2005,11(3):351-355.
[7] 邢联平,张倩,姚振强.破骨细胞介导炎症性骨丢失的研究进展[J]. 中华创伤骨科杂志,2006,8(7):671-674.
[8] Kartner N, Manolson MF. Novel techniques in the development of osteoporosis drug therapy: the osteoclast ruffled-border vacuolar H(+)-ATPase as an emerging target. Expert Opin Drug Discov.2014;9(5):505-522.
[9] Xiao YT, Xiang LX, Shao JZ. Vacuolar H(+)-ATPase.Int J Biochem Cell Biol.2008;40(10):2002-2006.
[10] Su Y, Zhou A, Al-Lamki R S, et al.The a-subunit of the V-type H+-ATPase interacts with phosphofructokinase-1 in humans. J Biol Chem.2003;278(22):20013-20018.
[11] Qin A, Cheng TS, Pavlos NJ, et al. V-ATPases in osteoclasts: structure, function and potential inhibitors of bone resorption. Int J Biochem Cell Biol.2012;44(9):1422-1435.
[12] Xu J, Cheng T, Feng HT, et al. Structure and function of V-ATPases in osteoclasts: potential therapeutic targets for the treatment of osteolysis.Histol Histopathol.2007; 22(4):443-454.
[13] Supanchart C, Kornak U. Ion channels and transporters in osteoclasts. Arch Biochem Biophys.2008;473(2): 161-165.
[14] Braun T, Zwerina J. Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. Arthritis Res Ther. 2011,13(4):235.
[15] Nieminen P, Morgan N V, Fenwick AL, et al. Inactivation of IL11 signaling causes craniosynostosis, delayed tooth eruption, and supernumerary teeth. Am J Hum Genet.2011; 89(1):67-81.
[16] Nakamura I, Jimi E. Regulation of osteoclast differentiation and function by interleukin-1. Vitam Horm.2006;74:357-370.
[17] Schilling B, Yeh J. Expression of transforming growth factor (TGF)-beta1, TGF-beta2, and TGF-beta3 and of type I and II TGF-beta receptors during the development of the human fetal ovary. Fertil Steril.1999;72(1):147-153.
[18] Katagiri T, Takahashi N. Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis.2002; 8(3):147-159.
[19] Kim N, Kadono Y, Takami M, et al. Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis. J Exp Med. 2005;202(5):589-595.
[20] Blair H C, Athanasou NA. Recent advances in osteoclast biology and pathological bone resorption. Histol Histopathol. 2004;19(1):189-199.
[21] Fujii T, Kitaura H, Kimura K, et al.IL-4 inhibits TNF-alpha- mediated osteoclast formation by inhibition of RANKL expression in TNF-alpha-activated stromal cells and direct inhibition of TNF-alpha-activated osteoclast precursors via a T-cell-independent mechanism in vivo. Bone. 2012;51(4): 771-780.
[22] Xu J, Cheng T, Feng HT, et al. Structure and function of V-ATPases in osteoclasts: potential therapeutic targets for the treatment of osteolysis. Histol Histopathol. 2007;22(4):443-454.
[23] Drory O, Nelson N. The emerging structure of vacuolar ATPases. Physiology (Bethesda).2006;21:317-325.
[24] Thudium CS, Jensen VK, Karsdal MA, et al.Disruption of the V-ATPase functionality as a way to uncouple bone formation and resorption - a novel target for treatment of osteoporosis. Curr Protein Pept Sci.2012;13(2):141-151.
[25] Nishi T, Kawasaki-Nishi S, Forgac M. Expression and function of the mouse V-ATPase d subunit isoforms. J Biol Chem. 2003; 278(47):46396-46402.
[26] Blake-Palmer KG, Su Y, Smith AN, et al. Molecular cloning and characterization of a novel form of the human vacuolar H+-ATPase e-subunit: an essential proton pump component. Gene.2007;393(1-2):94-100.
[27] Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol.2003;3(9):745-756.
[28] 陈如平,王昌兴,王伟东.类风湿性关节炎中肿瘤坏死因子α的表达及意义[J].医学综述,2011,17(5): 647-649.
[29] Sethi G, Sung B, Aggarwal BB. TNF: a master switch for inflammation to cancer. Front Biosci.2008;13:5094-5107.
[30] Black RA, Rauch CT, Kozlosky CJ, et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature.1997;385(6618):729-733.
[31] Osta B, Benedetti G, Miossec P. Classical and Paradoxical Effects of TNF-alpha on Bone Homeostasis. Front Immunol. 2014;5:48.
[32] Macewan DJ. TNF ligands and receptors--a matter of life and death. Br J Pharmacol.2002;135(4):855-875.
[33] Faustman D, Davis M.TNF receptor 2 pathway: drug target for autoimmune diseases. Nat Rev Drug Discov.2010;9(6): 482-493.
[34] Kudo O,Fujikawa Y,Itonaga I,et al.Proinflammatory cytokine (TNFalpha/IL-1alpha) induction of human osteoclast formation. J Pathol.2002;198(2):220-227.
[35] Mucci JM, Scian R, De Francesco PN, et al. Induction of osteoclastogenesis in an in vitro model of Gaucher disease is mediated by T cells via TNF-alpha. Gene.2012;509(1):51-59.
[36] Matsubara R, Kukita T, Ichigi Y, et al. Characterization and identification of subpopulations of mononuclear preosteoclasts induced by TNF-alpha in combination with TGF-beta in rats. PLoS One.2012;7(10):e47930.
[37] Kagiya T, Nakamura S.Expression profiling of microRNAs in RAW264.7 cells treated with a combination of tumor necrosis factor alpha and RANKL during osteoclast differentiation. J Periodontal Res.2013;48(3):373-385.
[38] Pacifici R.Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res. 1996;11(8): 1043-1051.
[39] 赵玉鸣,葛立宏,Grigoriadis Agi E.肿瘤坏死因子α对小鼠破骨细胞分化的影响[J].北京大学学报:医学版,2005,37(4): 433-435.
[40] Horowitz MC, Xi Y, Wilson K, et al. Control of osteoclastogenesis and bone resorption by members of the TNF family of receptors and ligands. Cytokine Growth Factor Rev.2001;12(1):9-18.
[41] Hofbauer LC, Heufelder AE. Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology.J Mol Med (Berl).2001;79(5-6):243-253.
[42] 孙嗣国,马保安,周勇,等.肿瘤坏死因子-α诱导外周血单核细胞分化为破骨细胞[J].第四军医大学学报,2005,(21):1988-1991.
[43] Fuller K, Murphy C, Kirstein B, et al. TNFalpha potently activates osteoclasts, through a direct action independent of and strongly synergistic with RANKL. Endocrinology. 2002; 143(3):1108-1118.