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Interleukin-10-Producing B Cells Help Suppress Ovariectomy-Mediated Osteoporosis

  • Yuhua Wang (Department of Prosthodontics, Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology) ;
  • Wei Zhang (Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University) ;
  • Seong-Min Lim (Department of Medical Biotechnology, Yeungnam University) ;
  • Li Xu (Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University) ;
  • Jun-O Jin (Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University)
  • Received : 2020.08.30
  • Accepted : 2020.10.21
  • Published : 2020.12.31

Abstract

Osteoporosis is prevalent in elderly women and it may cause dental implant failure. In particular, estrogen deficiency in postmenopausal women leads to higher rates of osteoporosis prevalence. Immune cell-mediated effects involving the development of osteoporosis have been studied previously; however, the role of IL-10-producing regulatory B (B10) cells in osteoporosis is largely unclear. Here, we examined the role of B10 cells in osteoporosis. C57BL/6 mice were subjected to ovariectomy (OVX). Fifteen weeks after OVX surgery, the first molar of the right maxillary was extracted, and twenty-four weeks after OVX surgery, serous progression of osteoporosis was observed in the alveolar bone. Moreover, the proportion of CD19+CD5+CD1dhigh regulatory B cells, B10, and CD4+CD25+FoxP3+ regulatory T cells from the spleen of OVX mice decreased during the progression of osteoporosis, compared to controls. In contrast to regulatory cells, IL-17-producing Th (Th17) cell levels were increased in OVX mice. Adoptive transfer of B10 cells to OVX mice led to a decrease in Th17 cell abundance and inhibited the development of osteoporosis in the alveolar bone from OVX mice. Thus, our results suggest that B10 cells may help suppress osteoporosis development.

Keywords

Acknowledgement

We thank the Shanghai Public Health Clinical Center animal facility for maintaining the animals used in this study. This study was supported by the National Research Foundation of Korea (NRF-2019R1C1C1003334 and NRF-2020R1A6A1A03044512) and the National Natural Science Foundation of China (81874164). Yuhua Wang was supported by the Shanghai Natural Science Foundation (20ZR1431900).

References

  1. Qaseem A, Forciea MA, McLean RM, Denberg TDClinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med 2017;166:818-839. https://doi.org/10.7326/M15-1361
  2. Roberts WE, Simmons KE, Garetto LP, DeCastro RA. Bone physiology and metabolism in dental implantology: risk factors for osteoporosis and other metabolic bone diseases. Implant Dent 1992;1:11-21. https://doi.org/10.1097/00008505-199200110-00002
  3. Sozen T, Ozisik L, Basaran NC. An overview and management of osteoporosis. Eur J Rheumatol 2017;4:46-56. https://doi.org/10.5152/eurjrheum.2016.048
  4. Cummings SR, Black DM, Nevitt MC, Browner W, Cauley J, Ensrud K, Genant HK, Palermo L, Scott J, Vogt TMThe Study of Osteoporotic Fractures Research Group. Bone density at various sites for prediction of hip fractures. Lancet 1993;341:72-75. https://doi.org/10.1016/0140-6736(93)92555-8
  5. Riggs BL. The mechanisms of estrogen regulation of bone resorption. J Clin Invest 2000;106:1203-1204. https://doi.org/10.1172/JCI11468
  6. Tella SH, Gallagher JC. Prevention and treatment of postmenopausal osteoporosis. J Steroid Biochem Mol Biol 2014;142:155-170. https://doi.org/10.1016/j.jsbmb.2013.09.008
  7. Newton-John HF, Morgan DB. The loss of bone with age, osteoporosis, and fractures. Clin Orthop Relat Res 1970;71:229-252. https://doi.org/10.1097/00003086-197007000-00029
  8. Sophocleous A, Idris AI. Rodent models of osteoporosis. Bonekey Rep 2014;3:614.
  9. Dar HY, Shukla P, Mishra PK, Anupam R, Mondal RK, Tomar GB, Sharma V, Srivastava RK. Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance. Bonekey Rep 2018;8:46-56. https://doi.org/10.1016/j.bonr.2018.02.001
  10. Clowes JA, Riggs BL, Khosla S. The role of the immune system in the pathophysiology of osteoporosis. Immunol Rev 2005;208:207-227. https://doi.org/10.1111/j.0105-2896.2005.00334.x
  11. Cenci S, Weitzmann MN, Roggia C, Namba N, Novack D, Woodring J, Pacifici R. Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-α. J Clin Invest 2000;106:1229-1237. https://doi.org/10.1172/JCI11066
  12. Zhao R. Immune regulation of osteoclast function in postmenopausal osteoporosis: a critical interdisciplinary perspective. Int J Med Sci 2012;9:825-832. https://doi.org/10.7150/ijms.5180
  13. Wang M, Tian T, Yu S, He N, Ma D. Th17 and Treg cells in bone related diseases. Clin Dev Immunol 2013;2013:203705.
  14. Monteleone I, Pallone F, Monteleone G. Th17-related cytokines: new players in the control of chronic intestinal inflammation. BMC Med 2011;9:122.
  15. Hashimoto M. Th17 in animal models of rheumatoid arthritis. J Clin Med 2017;6:73.
  16. Lorenzo J, Horowitz M, Choi Y. Osteoimmunology: interactions of the bone and immune system. Endocr Rev 2008;29:403-440. https://doi.org/10.1210/er.2007-0038
  17. Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses? Int Immunol 2009;21:1105-1111. https://doi.org/10.1093/intimm/dxp095
  18. Luo CY, Wang L, Sun C, Li DJ. Estrogen enhances the functions of CD4+CD25+Foxp3+ regulatory T cells that suppress osteoclast differentiation and bone resorption in vitro. Cell Mol Immunol 2011;8:50-58. https://doi.org/10.1038/cmi.2010.54
  19. Fischer L, Herkner C, Kitte R, Dohnke S, Riewaldt J, Kretschmer K, Garbe AI. Foxp3+ regulatory t cells in bone and hematopoietic homeostasis. Front Endocrinol (Lausanne) 2019;10:578.
  20. Atkinson SM, Hoffmann U, Hamann A, Bach E, Danneskiold-Samsoe NB, Kristiansen K, Serikawa K, Fox B, Kruse K, Haase C, et al. Depletion of regulatory T cells leads to an exacerbation of delayed-type hypersensitivity arthritis in C57BL/6 mice that can be counteracted by IL-17 blockade. Dis Model Mech 2016;9:427-440. https://doi.org/10.1242/dmm.022905
  21. Oh S, Rankin AL, Caton AJ. CD4+ CD25+  regulatory T cells in autoimmune arthritis. Immunol Rev 2010;233:97-111. https://doi.org/10.1111/j.0105-2896.2009.00848.x
  22. Haque M, Fino K, Lei F, Xiong X, Song J. Utilizing regulatory T cells against rheumatoid arthritis. Front Oncol 2014;4:209.
  23. O'Gradaigh D, Compston JE. T-cell involvement in osteoclast biology: implications for rheumatoid bone erosion. Rheumatology (Oxford) 2004;43:122-130. https://doi.org/10.1093/rheumatology/keg447
  24. Sokolov AV, Shmidt AA, Lomakin YA. B cell regulation in autoimmune diseases. Acta Naturae 2018;10:11-22. https://doi.org/10.32607/20758251-2018-10-3-11-22
  25. Chien CH, Chiang BL. Regulatory T cells induced by B cells: a novel subpopulation of regulatory T cells. J Biomed Sci 2017;24:86.
  26. Kalampokis I, Yoshizaki A, Tedder TF. IL-10-producing regulatory B cells (B10 cells) in autoimmune disease. Arthritis Res Ther 2013;15 Suppl 1:S1.
  27. Wang Y, Yu X, Lin J, Hu Y, Zhao Q, Kawai T, Taubman MA, Han X. B10 cells alleviate periodontal bone loss in experimental periodontitis. Infect Immun 2017;85:e00335-17.
  28. Figueredo CM, Lira-Junior R, Love RM. T and B cells in periodontal disease: new functions in a complex scenario. Int J Mol Sci 2019;20:3949.
  29. Kwak M, Yu K, Lee PC, Jin JO. Rehmannia glutinosa polysaccharide functions as a mucosal adjuvant to induce dendritic cell activation in mediastinal lymph node. Int J Biol Macromol 2018;120:1618-1623. https://doi.org/10.1016/j.ijbiomac.2018.09.187
  30. Park HB, Lim SM, Hwang J, Zhang W, You S, Jin JO. Cancer immunotherapy using a polysaccharide from Codium fragile in a murine model. OncoImmunology 2020;9:1772663.
  31. Zhang W, Xu L, Park HB, Hwang J, Kwak M, Lee PC, Liang G, Zhang X, Xu J, Jin JO. Escherichia coli adhesion portion FimH functions as an adjuvant for cancer immunotherapy. Nat Commun 2020;11:1187.
  32. Dar HY, Shukla P, Mishra PK, Anupam R, Mondal RK, Tomar GB, Sharma V, Srivastava RK. Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance. Bone Rep 2018;8:46-56. https://doi.org/10.1016/j.bonr.2018.02.001
  33. Hong M, Liao Y, Liang J, Chen X, Li S, Liu W, Gao C, Zhong Z, Kong D, Deng J, et al. Immunomodulation of human CD19+ CD25high regulatory B cells via Th17/Foxp3 regulatory T cells and Th1/Th2 cytokines. Hum Immunol 2019;80:863-870. https://doi.org/10.1016/j.humimm.2019.05.011
  34. Qiu X, Gui Y, Zhang N, Xu Y, Li D, Wang L. Effects of Bu-Shen-Ning-Xin Decoction on immune cells of the spleen and bone marrow in ovariectomized mice. Biosci Trends 2016;10:400-409. https://doi.org/10.5582/bst.2016.01012
  35. Onal M, Xiong J, Chen X, Thostenson JD, Almeida M, Manolagas SC, O'Brien CA. Receptor activator of nuclear factor κB ligand (RANKL) protein expression by B lymphocytes contributes to ovariectomyinduced bone loss. J Biol Chem 2012;287:29851-29860. https://doi.org/10.1074/jbc.M112.377945
  36. Debes GF, McGettigan SE. Skin-associated B cells in health and inflammation. J Immunol 2019;202:1659-1666. https://doi.org/10.4049/jimmunol.1801211
  37. Cain D, Kondo M, Chen H, Kelsoe G. Effects of acute and chronic inflammation on B-cell development and differentiation. J Invest Dermatol 2009;129:266-277. https://doi.org/10.1038/jid.2008.286
  38. Arron JR, Choi Y. Bone versus immune system. Nature 2000;408:535-536. https://doi.org/10.1038/35046196
  39. Kotake S, Nanke Y, Mogi M, Kawamoto M, Furuya T, Yago T, Kobashigawa T, Togari A, Kamatani N. IFN-gamma-producing human T cells directly induce osteoclastogenesis from human monocytes via the expression of RANKL. Eur J Immunol 2005;35:3353-3363. https://doi.org/10.1002/eji.200526141
  40. Palmqvist P, Lundberg P, Persson E, Johansson A, Lundgren I, Lie A, Conaway HH, Lerner UH. Inhibition of hormone and cytokine-stimulated osteoclastogenesis and bone resorption by interleukin-4 and interleukin-13 is associated with increased osteoprotegerin and decreased RANKL and RANK in a STAT6-dependent pathway. J Biol Chem 2006;281:2414-2429. https://doi.org/10.1074/jbc.M510160200
  41. Wei S, Wang MW, Teitelbaum SL, Ross FP. Interleukin-4 reversibly inhibits osteoclastogenesis via inhibition of NF-κB and mitogen-activated protein kinase signaling. J Biol Chem 2002;277:6622-6630. https://doi.org/10.1074/jbc.M104957200
  42. Mangashetti LS, Khapli SM, Wani MR. IL-4 inhibits bone-resorbing activity of mature osteoclasts by affecting NF-kappa B and Ca2+ signaling. J Immunol 2005;175:917-925. https://doi.org/10.4049/jimmunol.175.2.917
  43. Yuan FL, Li X, Lu WG, Zhao YQ, Li CW, Li JP, Sun JM, Xu RS. Type 17 T-helper cells might be a promising therapeutic target for osteoporosis. Mol Biol Rep 2012;39:771-774. https://doi.org/10.1007/s11033-011-0797-z
  44. Tyagi AM, Srivastava K, Mansoori MN, Trivedi R, Chattopadhyay N, Singh D. Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis. PLoS One 2012;7:e44552.
  45. Apse P, Ellen RP, Overall CM, Zarb GA. Microbiota and crevicular fluid collagenase activity in the osseointegrated dental implant sulcus: a comparison of sites in edentulous and partially edentulous patients. J Periodontal Res 1989;24:96-105. https://doi.org/10.1111/j.1600-0765.1989.tb00863.x
  46. Karoussis IK, Kotsovilis S, Fourmousis I. A comprehensive and critical review of dental implant prognosis in periodontally compromised partially edentulous patients. Clin Oral Implants Res 2007;18:669-679. https://doi.org/10.1111/j.1600-0501.2007.01406.x
  47. Holahan CM, Koka S, Kennel KA, Weaver AL, Assad DA, Regennitter FJ, Kademani D. Effect of osteoporotic status on the survival of titanium dental implants. Int J Oral Maxillofac Implants 2008;23:905-910.
  48. Chen H, Liu N, Xu X, Qu X, Lu E. Smoking, radiotherapy, diabetes and osteoporosis as risk factors for dental implant failure: a meta-analysis. PLoS One 2013;8:e71955.