PTH在治疗骨质疏松症及其作用机制的研究进展
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摘要
随着我国逐渐步入老龄化社会,骨质疏松症及其并发症将给社会带来巨大的负担。甲状旁腺激素(Parathyroid hormone,PTH)是由84个氨基酸组成的直链肽,与传统的抗骨质疏松药物不同,其可以调整骨转换状态,重塑骨小梁,使得骨量增加,降低骨质疏松骨折风险,因此在众多抗骨质疏松药物中备受关注。随着对PTH治疗骨质疏松症的研究不断深入,甲状旁腺相关肽PTHrP、甲状旁腺1型受体PTH1R、胰岛素样生长因子1(IGF-1)等先后被发现在PTH激活PTH1R抗骨质疏松中发挥作用,本文将有关研究进展做一综述。
As the population ages in our country, osteoporosis disease and its complications will bring huge burden to the society. Parathyroid hormone(PTH), which consists of 84 amino acids linear peptide, unlike traditional anti osteoporosis drug, can adjust the state of bone turnover, reshape the trabecular bone, which leads to increased bone mass and reduces the risk of osteoporosis fracture. Therefore it has attracted much attention in many anti osteoporosis drug.As the further study of PTH treatment of osteoporosis, parathyroid hormone-related peptide(PTHr P), parathyroid hormone type 1 receptor(PTH1R), insulin-like growth factor 1(IGF-1) have been discovered in the PTH activation PTH1 R anti osteoporosis function. This review is mean to illustrate the research progress briefly.
As the population ages in our country, osteoporosis disease and its complications will bring huge burden to the society. Parathyroid hormone(PTH), which consists of 84 amino acids linear peptide, unlike traditional anti osteoporosis drug, can adjust the state of bone turnover, reshape the trabecular bone, which leads to increased bone mass and reduces the risk of osteoporosis fracture. Therefore it has attracted much attention in many anti osteoporosis drug.As the further study of PTH treatment of osteoporosis, parathyroid hormone-related peptide(PTHr P), parathyroid hormone type 1 receptor(PTH1R), insulin-like growth factor 1(IGF-1) have been discovered in the PTH activation PTH1 R anti osteoporosis function. This review is mean to illustrate the research progress briefly.
引文
[1]Adler R A,El-Hajj F G,Bauer D C,et al.Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment:Report of a Task Force of the American Society for Bone and Mineral Research[J].Journal of Bone&Mineral Research the Official Journal of the American Society for Bone&Mineral Research,2015,31(1):16-35.
[2]Mehra T,Moos R M,Seifert B,et al.Impact of structural and economic factors on hospitalization costs,inpatient mortality,and treatment type of traumatic hip fractures in Switzerland[J].Archives of Osteoporosis,2017,12(1):7.
[3]Hernlund E,Svedbom A,Iverg?rd M,et al.Osteoporosis in the European Union:medical management,epidemiology and economic burden[J].Archives of Osteoporosis,2013,8(1):137.
[4]DarbàJ,Kaskens L,Pérezálvarez N,et al.Disability-adjusted-lifeyears losses in postmenopausal women with osteoporosis:a burden of illness study.[J].BMC Public Health,2015,15(1):1-10.
[5]Mccarthy J,Davis A.Diagnosis and Management of Vertebral Compression Fractures[J].American Family Physician,2016,94(1):44-50.
[6]Kanis J A,Burlet N,Cooper C,et al.European guidance for the diagnosis and management of osteoporosis in postmenopausal women[J].Osteoporosis International,2008,118(7):538-540.
[7]Lewiecki E.Prevention and treatment of postmenopausal osteoporosis[J].International Journal of Clinical Pharmacy,1998,20(5):198-205.
[8]Imai K.Alendronate sodium hydrate(oral jelly)for the treatment of osteoporosis:review of a novel,easy to swallow formulation[J].Clinical Interventions in Aging,2013,8:681-688.
[9]Rugpolmuang L,Waikakul S.Effect of a Short-Term Treatment with Once-A-Week Medication of Alendronate 70 Mg on Bone Turnover Markers in Postmenopausal Women with Osteoporosis[J].Journal of the Medical Association of Thailand=Chotmaihetthangphaet,2015,98(Suppl 8):70-75.
[10]Adler R A,El-Hajj F G,Bauer D C,et al.Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment:Report of a Task Force of the American Society for Bone and Mineral Research[J].Journal of Bone&Mineral Research the Official Journal of the American Society for Bone&Mineral Research,2015,31(1):16-35.
[11]Franceschi R T,Xiao G,Jiang D,et al.Multiple Signaling Pathways Converge on the Cbfa1/Runx2 Transcription Factor to Regulate Osteoblast Differentiation[J].Connective Tissue Research,2003,44Suppl 1(1):109-116.
[12]Cupp M E,Nayak S K,Adem A S,et al.Parathyroid hormone(PTH)and PTH-related peptide domains contributing to activation of different PTH receptor-mediated signaling pathways[J].Journal of Pharmacology&Experimental Therapeutics,2013,345(3):404-418.
[13]Matsumoto T,Itamochi S,Hashimoto Y.Effect of Concurrent Use of Whole-Body Vibration and Parathyroid Hormone on Bone Structure and Material Properties of Ovariectomized Mice[J].Calcified Tissue International,2016,98(5):1-10.
[14]Prank K,Nowlan S J,Harms H M,et al.Time series prediction of plasma hormone concentration.Evidence for differences in predictability of parathyroid hormone secretion between osteoporotic patients and normal controls[J].Journal of Clinical Investigation,1995,95(6):2910-2919.
[15]Shimizu M,Noda H,Joyashiki E,et al.The Optimal Duration of PTH(1-34)Infusion Is One Hour per Day to Increase Bone Mass in Rats[J].Biological&Pharmaceutical Bulletin,2016,39(4):625-630.
[16]Saini V,Marengi D A,Barry K J,et al.Parathyroid hormone(PTH)/PTH-related peptide type 1 receptor(PPR)signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH[J].Journal of Biological Chemistry,2013,288(28):20122-20134.
[17]Wein M N,Liang Y,Goransson O,et al.SIKs control osteocyte responses to parathyroid hormone[J].Nature Communications,2016,7:13176.
[18]Yang H,Dong J,Xiong W,et al.N-cadherin restrains PTH repressive effects on sclerostin/SOST by regulating LRP6-PTH1R interaction[J].Annals of the New York Academy of Sciences,2016,1385(1):41-52.
[19]Shimomura-Kuroki J,Farooq M,Sekimoto T,et al.Characteriza-tion of a PTH1R missense mutation responsible for Jansen type metaphyseal chondrodysplasia[J].Odontology,2016:1-5.
[20]Zindel D,Engel S,Bottrill A R,et al.Identification of key phosphorylation sites in PTH1R that determine arrestin3 binding and fine-tune receptor signaling[J].Biochemical Journal,2016,473(22):4173-4192.
[21]Varela A,Chouinard L,Lesage E,et al.One year of abaloparatide,a selective peptide activator of the PTH1 receptor,increased bone mass and strength in ovariectomized rats[J].Bone,2016,95:143-150.
[22]Leder B Z.Parathyroid Hormone and Parathyroid Hormone-Related Protein Analogs in Osteoporosis Therapy[J].Current Osteoporosis Reports:1-10.
[23]Chen Y,Bai B,Zhang S,et al.Effects of parathyroid hormone on calcium ions in rat bone marrow mesenchymal stem cells[J].Biomed Research International,2014,2014(6):751-759.
[24]Bellido T,Ali A A,Plotkin L I,et al.Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts.A putative explanation for why intermittent administration is needed for bone anabolism[J].Journal of Biological Chemistry,2004,278(50):50259-50272.
[25]Rodda S J,Mcmahon A P.Distinct roles for Hedgehog and canonical Wnt signaling in specification,differentiation and maintenance of osteoblast progenitors[J].Development,2006,133(16):3231-3244.
[26]Keller H,Kneissel M.SOST is a target gene for PTH in bone[J].Bone,2005,37(2):148-158.
[27]Costa N,Paramanathan S,Macdonald D,et al.Factors regulating circulating vascular endothelial growth factor(VEGF):association with bone mineral density(BMD)in post-menopausal osteoporosis[J].Cytokine,2009,46(3):376-381.
[2]Mehra T,Moos R M,Seifert B,et al.Impact of structural and economic factors on hospitalization costs,inpatient mortality,and treatment type of traumatic hip fractures in Switzerland[J].Archives of Osteoporosis,2017,12(1):7.
[3]Hernlund E,Svedbom A,Iverg?rd M,et al.Osteoporosis in the European Union:medical management,epidemiology and economic burden[J].Archives of Osteoporosis,2013,8(1):137.
[4]DarbàJ,Kaskens L,Pérezálvarez N,et al.Disability-adjusted-lifeyears losses in postmenopausal women with osteoporosis:a burden of illness study.[J].BMC Public Health,2015,15(1):1-10.
[5]Mccarthy J,Davis A.Diagnosis and Management of Vertebral Compression Fractures[J].American Family Physician,2016,94(1):44-50.
[6]Kanis J A,Burlet N,Cooper C,et al.European guidance for the diagnosis and management of osteoporosis in postmenopausal women[J].Osteoporosis International,2008,118(7):538-540.
[7]Lewiecki E.Prevention and treatment of postmenopausal osteoporosis[J].International Journal of Clinical Pharmacy,1998,20(5):198-205.
[8]Imai K.Alendronate sodium hydrate(oral jelly)for the treatment of osteoporosis:review of a novel,easy to swallow formulation[J].Clinical Interventions in Aging,2013,8:681-688.
[9]Rugpolmuang L,Waikakul S.Effect of a Short-Term Treatment with Once-A-Week Medication of Alendronate 70 Mg on Bone Turnover Markers in Postmenopausal Women with Osteoporosis[J].Journal of the Medical Association of Thailand=Chotmaihetthangphaet,2015,98(Suppl 8):70-75.
[10]Adler R A,El-Hajj F G,Bauer D C,et al.Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment:Report of a Task Force of the American Society for Bone and Mineral Research[J].Journal of Bone&Mineral Research the Official Journal of the American Society for Bone&Mineral Research,2015,31(1):16-35.
[11]Franceschi R T,Xiao G,Jiang D,et al.Multiple Signaling Pathways Converge on the Cbfa1/Runx2 Transcription Factor to Regulate Osteoblast Differentiation[J].Connective Tissue Research,2003,44Suppl 1(1):109-116.
[12]Cupp M E,Nayak S K,Adem A S,et al.Parathyroid hormone(PTH)and PTH-related peptide domains contributing to activation of different PTH receptor-mediated signaling pathways[J].Journal of Pharmacology&Experimental Therapeutics,2013,345(3):404-418.
[13]Matsumoto T,Itamochi S,Hashimoto Y.Effect of Concurrent Use of Whole-Body Vibration and Parathyroid Hormone on Bone Structure and Material Properties of Ovariectomized Mice[J].Calcified Tissue International,2016,98(5):1-10.
[14]Prank K,Nowlan S J,Harms H M,et al.Time series prediction of plasma hormone concentration.Evidence for differences in predictability of parathyroid hormone secretion between osteoporotic patients and normal controls[J].Journal of Clinical Investigation,1995,95(6):2910-2919.
[15]Shimizu M,Noda H,Joyashiki E,et al.The Optimal Duration of PTH(1-34)Infusion Is One Hour per Day to Increase Bone Mass in Rats[J].Biological&Pharmaceutical Bulletin,2016,39(4):625-630.
[16]Saini V,Marengi D A,Barry K J,et al.Parathyroid hormone(PTH)/PTH-related peptide type 1 receptor(PPR)signaling in osteocytes regulates anabolic and catabolic skeletal responses to PTH[J].Journal of Biological Chemistry,2013,288(28):20122-20134.
[17]Wein M N,Liang Y,Goransson O,et al.SIKs control osteocyte responses to parathyroid hormone[J].Nature Communications,2016,7:13176.
[18]Yang H,Dong J,Xiong W,et al.N-cadherin restrains PTH repressive effects on sclerostin/SOST by regulating LRP6-PTH1R interaction[J].Annals of the New York Academy of Sciences,2016,1385(1):41-52.
[19]Shimomura-Kuroki J,Farooq M,Sekimoto T,et al.Characteriza-tion of a PTH1R missense mutation responsible for Jansen type metaphyseal chondrodysplasia[J].Odontology,2016:1-5.
[20]Zindel D,Engel S,Bottrill A R,et al.Identification of key phosphorylation sites in PTH1R that determine arrestin3 binding and fine-tune receptor signaling[J].Biochemical Journal,2016,473(22):4173-4192.
[21]Varela A,Chouinard L,Lesage E,et al.One year of abaloparatide,a selective peptide activator of the PTH1 receptor,increased bone mass and strength in ovariectomized rats[J].Bone,2016,95:143-150.
[22]Leder B Z.Parathyroid Hormone and Parathyroid Hormone-Related Protein Analogs in Osteoporosis Therapy[J].Current Osteoporosis Reports:1-10.
[23]Chen Y,Bai B,Zhang S,et al.Effects of parathyroid hormone on calcium ions in rat bone marrow mesenchymal stem cells[J].Biomed Research International,2014,2014(6):751-759.
[24]Bellido T,Ali A A,Plotkin L I,et al.Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts.A putative explanation for why intermittent administration is needed for bone anabolism[J].Journal of Biological Chemistry,2004,278(50):50259-50272.
[25]Rodda S J,Mcmahon A P.Distinct roles for Hedgehog and canonical Wnt signaling in specification,differentiation and maintenance of osteoblast progenitors[J].Development,2006,133(16):3231-3244.
[26]Keller H,Kneissel M.SOST is a target gene for PTH in bone[J].Bone,2005,37(2):148-158.
[27]Costa N,Paramanathan S,Macdonald D,et al.Factors regulating circulating vascular endothelial growth factor(VEGF):association with bone mineral density(BMD)in post-menopausal osteoporosis[J].Cytokine,2009,46(3):376-381.