T淋巴细胞参与调节甲状旁腺激素对骨代谢的作用
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摘要
骨免疫学是研究骨代谢和免疫学之间相互作用的交叉学科,骨髓中T淋巴细胞参与了调节骨代谢的一系列反应。近年来,动物实验及临床试验结果提示:T淋巴细胞不仅可以直接分泌促进骨吸收和骨形成的细胞因子,还可以通过参与调节核因子κB受体活化因子配体(receptor activator of NF-κB ligand,RANKL)/骨保护素(osteoprotegerin, OPG)、 Wnt等信号通路,调节骨髓基质细胞对甲状旁腺激素(parathyroid hormone,PTH)的反应,从而影响PTH的作用。本文回顾近年来的研究结果,就T淋巴细胞参与调节PTH相关作用做一综述。
Osteoimmunology is an interdiscipline studying the association between bone metabolism and immunology,and T lymphocyte in marrow cavity participates in regulating bone metabolism. In recent years,both animal experiments and clinical trials showed that T lymphocyte could not only secrete cytokines to regulate bone absorption and formation,but also could play a role in receptor activator of NF-κB ligand( RANKL)/osteoprotegerin( OPG),Wnt pathways to regulate bone marrow stromal cells reacting to parathyroid hormone( PTH). This literature review the results of recent years and discuss T lymphocyte involved in bone metabolism regulated by PTH.
Osteoimmunology is an interdiscipline studying the association between bone metabolism and immunology,and T lymphocyte in marrow cavity participates in regulating bone metabolism. In recent years,both animal experiments and clinical trials showed that T lymphocyte could not only secrete cytokines to regulate bone absorption and formation,but also could play a role in receptor activator of NF-κB ligand( RANKL)/osteoprotegerin( OPG),Wnt pathways to regulate bone marrow stromal cells reacting to parathyroid hormone( PTH). This literature review the results of recent years and discuss T lymphocyte involved in bone metabolism regulated by PTH.
引文
[1]Grey AB,Stapleton JP,Evans MC,et al.Accelerated bone loss in post-menopausal women with mild primary hyperparathyroidism[J].Clin Endocrinol(Oxf),1996,44:697-702.
[2]Walker MD,Dempster DW,Mcmahon DJ,et al.Effect of renal function on skeletal health in primary hyperparathyroidism[J].J Clin Endocrinol Metab,2012,97:1501-1507.
[3]Altman-Singles AR,Jeong Y,Tseng WJ,et al.Intermittent Parathyroid Hormone after Prolonged Alendronate Treatment Induces Substantial New Bone Formation and Increases Bone Tissue Heterogeneity in Ovariectomized Rats[J].J Bone Miner Res,2017,32:1703-1715.
[4]Criscitiello C,Viale G,Gelao L,et al.Crosstalk between bone niche and immune system:Osteoim-munology signaling as a potential target for cancer treatment[J].Cancer Treatment Reviews,2015,41:61-68.
[5]Kong YY,Feige U,Sarosi I,et al.Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand[J].Nature,1999,402:304-309.
[6]Ding C,Parameswaran V,Udayan R,et al.Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults:a longitudinal study[J].J Clin Endocrinol Metab,2008,93:1952-1958.
[7]Pasco JA,Kotowicz MA,Henry MJ,et al.High-sensitivity C-reactive protein and fracture risk in elderly women[J].JAMA,2006,296:1353-1355.
[8]Eriksson AL,Moverare-Skrtic S,Ljunggren O,et al.High-sensitivity CRP is an independent risk factor for all fractures and vertebral fractures in elderly men:the MrOS Sweden study[J].J Bone Miner Res,2014,29:418-423.
[9]Wolf M,Lossdorfer S,Marciniak J,et al.CD8+T cells mediate the regenerative PTH effect in h PDL cells via Wnt10b signaling[J].Innate Immun,2016,22:674-681.
[10]Qin L,Raggatt LJ,Partridge NC.Parathyroid hormone:a double-edged sword for bone metabolism[J].Trends Endocrinol Metab,2004,15:60-65.
[11]Huang JC,Sakata T,Pfleger LL,et al.PTH differentially regulates expression of RANKL and OPG[J].JBone Miner Res,2004,19:235-244.
[12]Glass DN,Karsenty G.In vivo analysis of Wnt signaling in bone[J].Endocrinology,2007,148:2630-2634.
[13]Keller H,Kneissel M.SOST is a target gene for PTHin bone[J].Bone,2005,37:148-158.
[14]Bedi B,Li JY,Tawfeek H,et al.Silencing of parathyroid hormone(PTH)receptor 1 in T cells blunts the bone anabolic activity of PTH[J].Proc Natl Acad Sci USA,2012,109:E725-E733.
[15]Tobimatsu T,Kaji H,Sowa H,et al.Parathyroid hormone increases beta-catenin levels through Smad3 in mouse osteoblastic cells[J].Endocrinology,2006,147:2583-2590.
[16]Di Rosa F,Pabst R.The bone marrow:a nest for migratory memory T cells[J].Trends Immunol,2005,26:360-366.
[17]D'Amelio P,Grimaldi A,Di Bella S,et al.Estrogen deficiency increases osteoclastogenesis up-regulating Tcells activity:a key mechanism in osteoporosis[J].Bone,2008,43:92-100.
[18]Hory BG,Roussanne MC,Rostand S,et al.Absence of response to human parathyroid hormone in athymic mice grafted with human parathyroid adenoma,hyperplasia or parathyroid cells maintained in culture[J].JEndocrinol Invest,2000,23:273-279.
[19]Gao Y,Wu X,Terauchi M,et al.T cells potentiate PTH-induced cortical bone loss through CD40Lsignaling[J].Cell Metab,2008,8:132-145.
[20]Tawfeek H,Bedi B,Li JY,et al.Disruption of PTHreceptor 1 in T cells protects against PTH-induced bone loss[J].PLoS One,2010,5:e12290.
[21]Ben-Awadh AN,Delgado-Calle J,Tu X,et al.Parathyroid hormone receptor signaling induces bone resorption in the adult skeleton by directly regulating the RANKL gene in osteocytes[J].Endocrinology,2014,155:2797-2809.
[22]Cho SW,Pirih FQ,Koh AJ,et al.The soluble interleukin-6 receptor is a mediator of hematopoietic and skeletal actions of parathyroid hormone[J].J Biol Chem,2013,288:6814-6825.
[23]Basu R,Hatton RD,Weaver CT.The Th17 family:flexibility follows function[J].Immunol Rev,2013,252:89-103.
[24]Bettelli E,Carrier Y,Gao W,et al.Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells[J].Nature,2006,441:235-238.
[25]Miossec P,Korn T,Kuchroo VK.Interleukin-17 and type 17 helper T cells[J].N Engl J Med,2009,361:888-898.
[26]Li JY,D'Amelio P,Robinson J,et al.IL-17A is increased in humans with primary hyperparathyroidism and mediates PTH-induced bone loss in mice[J].Cell Metab,2015,22:799-810.
[27]Terauchi M,Li JY,Bedi B,et al.T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling[J].Cell Metab,2009,10:229-240.
[28]Terauchi M,Li JY,Bedi B,et al.T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling[J].Cell Metab,2009,10:229-240.
[29]Pettway GJ,Schneider A,Koh AJ,et al.Anabolic actions of PTH(1-34):use of a novel tissue engineering model to investigate temporal effects on bone[J].Bone,2005,36:959-970.
[30]Langdahl BL,Libanati C,Crittenden DB,et al.Romosozumab(sclerostin monoclonal antibody)versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy:a randomised,open-label,phase 3 trial[J].Lancet,2017,30:1585-1594
[31]Bianchi ML,Duca P,Vai S,et al.Improving adherence to and persistence with oral therapy of osteoporosis[J].Osteoporos Int,2015,26:1629-1638.
[32]Young N,Mikhalkevich N,Yan Y,et al.Differential regulation of osteoblast activity by Th cell subsets mediated by parathyroid hormone and IFN-gamma[J].JImmunol,2005,175:8287-8295.
[2]Walker MD,Dempster DW,Mcmahon DJ,et al.Effect of renal function on skeletal health in primary hyperparathyroidism[J].J Clin Endocrinol Metab,2012,97:1501-1507.
[3]Altman-Singles AR,Jeong Y,Tseng WJ,et al.Intermittent Parathyroid Hormone after Prolonged Alendronate Treatment Induces Substantial New Bone Formation and Increases Bone Tissue Heterogeneity in Ovariectomized Rats[J].J Bone Miner Res,2017,32:1703-1715.
[4]Criscitiello C,Viale G,Gelao L,et al.Crosstalk between bone niche and immune system:Osteoim-munology signaling as a potential target for cancer treatment[J].Cancer Treatment Reviews,2015,41:61-68.
[5]Kong YY,Feige U,Sarosi I,et al.Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand[J].Nature,1999,402:304-309.
[6]Ding C,Parameswaran V,Udayan R,et al.Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults:a longitudinal study[J].J Clin Endocrinol Metab,2008,93:1952-1958.
[7]Pasco JA,Kotowicz MA,Henry MJ,et al.High-sensitivity C-reactive protein and fracture risk in elderly women[J].JAMA,2006,296:1353-1355.
[8]Eriksson AL,Moverare-Skrtic S,Ljunggren O,et al.High-sensitivity CRP is an independent risk factor for all fractures and vertebral fractures in elderly men:the MrOS Sweden study[J].J Bone Miner Res,2014,29:418-423.
[9]Wolf M,Lossdorfer S,Marciniak J,et al.CD8+T cells mediate the regenerative PTH effect in h PDL cells via Wnt10b signaling[J].Innate Immun,2016,22:674-681.
[10]Qin L,Raggatt LJ,Partridge NC.Parathyroid hormone:a double-edged sword for bone metabolism[J].Trends Endocrinol Metab,2004,15:60-65.
[11]Huang JC,Sakata T,Pfleger LL,et al.PTH differentially regulates expression of RANKL and OPG[J].JBone Miner Res,2004,19:235-244.
[12]Glass DN,Karsenty G.In vivo analysis of Wnt signaling in bone[J].Endocrinology,2007,148:2630-2634.
[13]Keller H,Kneissel M.SOST is a target gene for PTHin bone[J].Bone,2005,37:148-158.
[14]Bedi B,Li JY,Tawfeek H,et al.Silencing of parathyroid hormone(PTH)receptor 1 in T cells blunts the bone anabolic activity of PTH[J].Proc Natl Acad Sci USA,2012,109:E725-E733.
[15]Tobimatsu T,Kaji H,Sowa H,et al.Parathyroid hormone increases beta-catenin levels through Smad3 in mouse osteoblastic cells[J].Endocrinology,2006,147:2583-2590.
[16]Di Rosa F,Pabst R.The bone marrow:a nest for migratory memory T cells[J].Trends Immunol,2005,26:360-366.
[17]D'Amelio P,Grimaldi A,Di Bella S,et al.Estrogen deficiency increases osteoclastogenesis up-regulating Tcells activity:a key mechanism in osteoporosis[J].Bone,2008,43:92-100.
[18]Hory BG,Roussanne MC,Rostand S,et al.Absence of response to human parathyroid hormone in athymic mice grafted with human parathyroid adenoma,hyperplasia or parathyroid cells maintained in culture[J].JEndocrinol Invest,2000,23:273-279.
[19]Gao Y,Wu X,Terauchi M,et al.T cells potentiate PTH-induced cortical bone loss through CD40Lsignaling[J].Cell Metab,2008,8:132-145.
[20]Tawfeek H,Bedi B,Li JY,et al.Disruption of PTHreceptor 1 in T cells protects against PTH-induced bone loss[J].PLoS One,2010,5:e12290.
[21]Ben-Awadh AN,Delgado-Calle J,Tu X,et al.Parathyroid hormone receptor signaling induces bone resorption in the adult skeleton by directly regulating the RANKL gene in osteocytes[J].Endocrinology,2014,155:2797-2809.
[22]Cho SW,Pirih FQ,Koh AJ,et al.The soluble interleukin-6 receptor is a mediator of hematopoietic and skeletal actions of parathyroid hormone[J].J Biol Chem,2013,288:6814-6825.
[23]Basu R,Hatton RD,Weaver CT.The Th17 family:flexibility follows function[J].Immunol Rev,2013,252:89-103.
[24]Bettelli E,Carrier Y,Gao W,et al.Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells[J].Nature,2006,441:235-238.
[25]Miossec P,Korn T,Kuchroo VK.Interleukin-17 and type 17 helper T cells[J].N Engl J Med,2009,361:888-898.
[26]Li JY,D'Amelio P,Robinson J,et al.IL-17A is increased in humans with primary hyperparathyroidism and mediates PTH-induced bone loss in mice[J].Cell Metab,2015,22:799-810.
[27]Terauchi M,Li JY,Bedi B,et al.T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling[J].Cell Metab,2009,10:229-240.
[28]Terauchi M,Li JY,Bedi B,et al.T lymphocytes amplify the anabolic activity of parathyroid hormone through Wnt10b signaling[J].Cell Metab,2009,10:229-240.
[29]Pettway GJ,Schneider A,Koh AJ,et al.Anabolic actions of PTH(1-34):use of a novel tissue engineering model to investigate temporal effects on bone[J].Bone,2005,36:959-970.
[30]Langdahl BL,Libanati C,Crittenden DB,et al.Romosozumab(sclerostin monoclonal antibody)versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy:a randomised,open-label,phase 3 trial[J].Lancet,2017,30:1585-1594
[31]Bianchi ML,Duca P,Vai S,et al.Improving adherence to and persistence with oral therapy of osteoporosis[J].Osteoporos Int,2015,26:1629-1638.
[32]Young N,Mikhalkevich N,Yan Y,et al.Differential regulation of osteoblast activity by Th cell subsets mediated by parathyroid hormone and IFN-gamma[J].JImmunol,2005,175:8287-8295.