Wnt/β-catenin信号通路在补肾中药靶向治疗骨质疏松症中应用的研究进展
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摘要
骨质疏松症是以骨质量降低、脆性增加为主要病理特征的全身代谢性骨病,其发病受多种因素的影响。随着我国人口老龄化加速,骨质疏松症发病率明显上升,其严重的并发症及较高的治疗费用给患者及社会带来严重的负担。近年来随着分子生物学的发展,对信号通路蛋白及基因的研究不断深入,发现Wnt/β-catenin通路在骨形成中发挥着重要的作用,本文将基于Wnt/β-catenin信号通路在骨质疏松症的发生及中药靶向治疗骨质疏松的研究概况方面做一综述,旨在为骨质疏松症的发病机制及精准靶向治疗提供一定的参考,为中药多靶点治疗骨质疏松症的独特优势提供新思路。
Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass and increased brittleness, and its onset is affected by many factors. With the accelerated aging in the Chinese population, the incidence of osteoporosis has risen significantly, and its severe complications and high treatment costs have brought serious burdens to patients and the society. In recent years, with the development of molecular biology, the research on signaling pathway proteins and genes has been advanced, and it has been found that the Wnt/β-catenin pathway plays an important role in bone formation. This article reviewed the research progress of Wnt/β-catenin signaling pathway in the pathogenesis of osteoporosis and the targeted treatment of osteoporosis with traditional Chinese medicine, with the aim of providing certain references for the pathogenesis of osteoporosis and precise targeted therapy, and new ideas for exerting the unique advantages of traditional Chinese medicine of multi-target treatment of osteoporosis.
Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass and increased brittleness, and its onset is affected by many factors. With the accelerated aging in the Chinese population, the incidence of osteoporosis has risen significantly, and its severe complications and high treatment costs have brought serious burdens to patients and the society. In recent years, with the development of molecular biology, the research on signaling pathway proteins and genes has been advanced, and it has been found that the Wnt/β-catenin pathway plays an important role in bone formation. This article reviewed the research progress of Wnt/β-catenin signaling pathway in the pathogenesis of osteoporosis and the targeted treatment of osteoporosis with traditional Chinese medicine, with the aim of providing certain references for the pathogenesis of osteoporosis and precise targeted therapy, and new ideas for exerting the unique advantages of traditional Chinese medicine of multi-target treatment of osteoporosis.
引文
[1] Stevens JA,Rudd RA.The impact of decreasing U.S.hip fracture rates on future hip fracture estimates [J].Osteoporos Int, 2013, 24(10):2725-2728.
[2] 张智海,张智若,刘忠厚,等.中国大陆地区以-2.0SD为诊断标准的骨质疏松症发病率文献回顾性研究[J].中国骨质疏松杂志, 2016, 22(1):1-8.
[3] Kyllonen L, D Este M, Alini M,et al.Local drug delivery forenhancing fracture healing in osteoporotic bone [J].Acta Biomater, 2015,11(1):412-434.
[4] Liu Z,Weaver J,De Papp A,et al.Disparities in osteoporosis treatments [J].Osteoporos Int, 2016, 27(2):509-519.
[5] 李建国,白璧辉,谢兴文,等.绝经后骨质疏松症发病相关因素分析及治疗进展[J].辽宁中医药大学学报,2018,20(11):97-100.
[6] Yu W, Zhang Y,Yu L,et al.Micoarray-based bioinformaticsanalysis of osteoblasts on Tio2nanotube layers[J].Colloids and Surfaces B:Biointer faces, 2012, 93:135-142.
[7] Zhang R.Oyajobi BO,Harris S,et al.Wnt/β-catenin singnaling cativates bone morphogengtic protenin expression in osteoblasts[J].Bone, 2013, 52(1):145-156.
[8] Chen S,Feng J,Bao Q,et al.Adverse effects of osteo-cytic constitutive activation of β-catenin on bone strength and bone growth[J].J Bone Miner Res, 2015, 30(7):1184-1194.
[9] Dees C,Distler JH.Canonical Wnt signaling as a key regulator of fibroge-nesis-implications for targeted therapies?[J].Exp Dermatol, 2013, 22(11):710-713.
[10] Anastas JN,Moon RT. WNT signalling pathways as therapeutic targets in cancer[J]. Nat Rev Cancer, 2013,13(1):11-26.
[11] 阮立奇,黄波.Wnt/β-catenin信号通路在去睾丸小鼠骨质疏松发病中的作用[J].温州医科大学学报, 2017, 47(7):519-522.
[12] Li B,Zhang H,Zeng M,et al.Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide-induced apoptosis partially by inhibiting the Wnt/β-catenin pathway[J].Cell Biol Int, 2015, 39(2):192-200.
[13] Lu XM,Zhao H, Wang EH. A high-fat diet induces obesity and impairs bone acquisition in young male mice[J]. Mol Med Rep, 2013, 7(4): 1203-1208.
[14] Glassd A,Karsenty G.In vivo analysis of Wnt sig-naling in bone[J]. Endocrinology, 2007, 148(6):2630-2634.
[15] 李建国,谢兴文,李鼎鹏,等.中药淫羊藿治疗骨质疏松症的研究进展[J].中国骨质疏松杂志, 2018, 24(3):389-393.
[16] Zhang JF,Li G,Chan CY,et al.Flavonoids of HerbaEpimedii regulate osteogenesis of human mesenchymal stem cells through BMP and Wnt / beta-catenin signalingpathway[J]. Mol Cell Endocrinol, 2010, 314 (1):70-74.
[17] Li XF,Xu H,Zhao YJ,et al.Icariin augments bone formation and reverses the phenotypes of osteoprotegerin deficient mice through the activation of Wnt /β-Catenin-BMP ignaling[J]. Evid Based Complement Alternat Med,2013, 2013: 652317.
[18] 涂艳,熊莉娜,柳湘洁,等.淫羊藿苷对成骨细胞成骨分化的影响及Wnt/-catenin信号系统的关系研究[J].中国中医急症, 2017, 26(3):448-450, 466.
[19] 曾建春,曾意荣,樊粤光,等.淫羊藿甙诱导MSCs向成骨细胞分化过程中对Wnt信号通路的影响[J].广州中医药大学学报, 2014, 31(4):607-611.
[20] 袁真,闵珺,王恺,等.杜仲黄酮类3种药物成分治疗大鼠骨质疏松的比较研究[J].中国骨质疏松杂志, 2018, 24(2):244-248.
[21] 汤军.杜仲醇提取物诱导大鼠骨髓间充质干细胞成骨分化中Wnt信号通路研究[D].南京中医药大学,2013.
[22] 张贤,朱丽华,钱晓伟,等.杜仲醇提取物诱导骨髓间充质干细胞成骨分化中的Wnt信号途径[J].中国组织工程研究, 2012, 16 (45):8520-8523.
[23] 唐德志,侯炜,周泉,等.蛇床子素通过激活并转入β-Cate-nin-BMP 信号途径而促进成骨细胞分化和骨形成[C].第八届国际骨矿研究学术会议暨第十届国际骨质疏松研讨会论文集, 2010,11.
[24] 郑苏阳.基于内质网应激与Wnt/β-catenin信号通路研究蛇床子素对成骨细胞增殖与分化的影响及机制[D].南京中医药大学,2017.
[25] 李玲慧,丁道芳,杜国庆,等.蛇床子素对新生大鼠成骨细胞增殖的影响及相关机制研究[J].中国骨伤, 2013, 26(5):419-422.
[26] 郭英,李佩芳,舒晓春,等.骨碎补总黄酮对骨髓间充质干细胞成骨分化过程中 Wnt/β-catenin 信号通路的影响[J].中华医学杂志, 2012, 92 (32):2288-2291.
[27] Ma X,Lv J,Sun X,et al.Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3Aexpression in denervated bone[J].Sci Rep, 2016,6: 24562.
[28] Lv J,Sun X,Ma J,et al.Involvement of periostin-sclerostin-Wnt /β-catenin signaling pathway in the prevention of neurectomy-induced bone loss by naringin[J].Biochem Biophys Res Commun, 2015,468 (4):587-593.
[29] Wang D,Ma W,Wang F,et al.Stimulation of Wnt/β-Catenin Signaling to Improve Bone Development by Naringin via Interacting with AMPK and Akt[J].Cell Physiol Biochem, 2015, 36(4):1563-1576.
[30] 陈云刚,谭国庆,任维龙,等.骨碎补含药血清经wnt/β-catenin信号通路对大鼠骨髓间充质干细胞成骨分化的影响[J].中国药理学通报, 2017, 33(6):830-836.
[31] 洪郭驹,陈鹏,韩晓蕊,等.复方贞术调脂胶囊调控MEKK2-Wnt偶联拮抗β-catenin泛素化改善大鼠糖皮质激素骨质疏松症[J].中国实验动物学报, 2018, 26(1):36-44.
[32] 沈霖,马陈,帅波,等.青娥丸对绝经后骨质疏松症患者β-catenin和DKK-1表达水平的影响[J].中西医结合研究, 2016, 8(6):281-284.
[33] 杨军,莫新民.壮骨止痛方对骨质疏松大鼠Wnt/β-catenin信号通路、血清Sclerostin水平的影响[J].中医药通报, 2017, 16(3):67-69.
[34] 马苟平.基于经典Wnt-β-catenin通路六味地黄丸抗去势大鼠骨质疏松作用的机制研究[D].浙江中医药大学, 2015.
[35] 李建国,谢兴文,李宁,等.中医非药物治疗原发性骨质疏松症的临床研究概况[J].中国骨质疏松杂志,2018,24(9):1250-1254.
[36] 刘海龙,卫荣.绝经后骨质疏松症中西医临床治疗进展[J].现代中西医结合杂志, 2014, 23(14):1594-1596.
[37] Tohda C, Nagata A. Epimedium koreanum Extract and Its Constituent Icariin Improve Motor Dysfunction in Spinal Cord Injury[J].Evidence-based Complementary and Alternative Medicine, 2012, 7(9):1208.
[38] 李翠娟,巩振东,崔馨文,等.Wnt信号通路与骨质疏松症发病关系及中医药治疗研究进展[J].现代中医药, 2016, 36(2):97-100.
[2] 张智海,张智若,刘忠厚,等.中国大陆地区以-2.0SD为诊断标准的骨质疏松症发病率文献回顾性研究[J].中国骨质疏松杂志, 2016, 22(1):1-8.
[3] Kyllonen L, D Este M, Alini M,et al.Local drug delivery forenhancing fracture healing in osteoporotic bone [J].Acta Biomater, 2015,11(1):412-434.
[4] Liu Z,Weaver J,De Papp A,et al.Disparities in osteoporosis treatments [J].Osteoporos Int, 2016, 27(2):509-519.
[5] 李建国,白璧辉,谢兴文,等.绝经后骨质疏松症发病相关因素分析及治疗进展[J].辽宁中医药大学学报,2018,20(11):97-100.
[6] Yu W, Zhang Y,Yu L,et al.Micoarray-based bioinformaticsanalysis of osteoblasts on Tio2nanotube layers[J].Colloids and Surfaces B:Biointer faces, 2012, 93:135-142.
[7] Zhang R.Oyajobi BO,Harris S,et al.Wnt/β-catenin singnaling cativates bone morphogengtic protenin expression in osteoblasts[J].Bone, 2013, 52(1):145-156.
[8] Chen S,Feng J,Bao Q,et al.Adverse effects of osteo-cytic constitutive activation of β-catenin on bone strength and bone growth[J].J Bone Miner Res, 2015, 30(7):1184-1194.
[9] Dees C,Distler JH.Canonical Wnt signaling as a key regulator of fibroge-nesis-implications for targeted therapies?[J].Exp Dermatol, 2013, 22(11):710-713.
[10] Anastas JN,Moon RT. WNT signalling pathways as therapeutic targets in cancer[J]. Nat Rev Cancer, 2013,13(1):11-26.
[11] 阮立奇,黄波.Wnt/β-catenin信号通路在去睾丸小鼠骨质疏松发病中的作用[J].温州医科大学学报, 2017, 47(7):519-522.
[12] Li B,Zhang H,Zeng M,et al.Bone marrow mesenchymal stem cells protect alveolar macrophages from lipopolysaccharide-induced apoptosis partially by inhibiting the Wnt/β-catenin pathway[J].Cell Biol Int, 2015, 39(2):192-200.
[13] Lu XM,Zhao H, Wang EH. A high-fat diet induces obesity and impairs bone acquisition in young male mice[J]. Mol Med Rep, 2013, 7(4): 1203-1208.
[14] Glassd A,Karsenty G.In vivo analysis of Wnt sig-naling in bone[J]. Endocrinology, 2007, 148(6):2630-2634.
[15] 李建国,谢兴文,李鼎鹏,等.中药淫羊藿治疗骨质疏松症的研究进展[J].中国骨质疏松杂志, 2018, 24(3):389-393.
[16] Zhang JF,Li G,Chan CY,et al.Flavonoids of HerbaEpimedii regulate osteogenesis of human mesenchymal stem cells through BMP and Wnt / beta-catenin signalingpathway[J]. Mol Cell Endocrinol, 2010, 314 (1):70-74.
[17] Li XF,Xu H,Zhao YJ,et al.Icariin augments bone formation and reverses the phenotypes of osteoprotegerin deficient mice through the activation of Wnt /β-Catenin-BMP ignaling[J]. Evid Based Complement Alternat Med,2013, 2013: 652317.
[18] 涂艳,熊莉娜,柳湘洁,等.淫羊藿苷对成骨细胞成骨分化的影响及Wnt/-catenin信号系统的关系研究[J].中国中医急症, 2017, 26(3):448-450, 466.
[19] 曾建春,曾意荣,樊粤光,等.淫羊藿甙诱导MSCs向成骨细胞分化过程中对Wnt信号通路的影响[J].广州中医药大学学报, 2014, 31(4):607-611.
[20] 袁真,闵珺,王恺,等.杜仲黄酮类3种药物成分治疗大鼠骨质疏松的比较研究[J].中国骨质疏松杂志, 2018, 24(2):244-248.
[21] 汤军.杜仲醇提取物诱导大鼠骨髓间充质干细胞成骨分化中Wnt信号通路研究[D].南京中医药大学,2013.
[22] 张贤,朱丽华,钱晓伟,等.杜仲醇提取物诱导骨髓间充质干细胞成骨分化中的Wnt信号途径[J].中国组织工程研究, 2012, 16 (45):8520-8523.
[23] 唐德志,侯炜,周泉,等.蛇床子素通过激活并转入β-Cate-nin-BMP 信号途径而促进成骨细胞分化和骨形成[C].第八届国际骨矿研究学术会议暨第十届国际骨质疏松研讨会论文集, 2010,11.
[24] 郑苏阳.基于内质网应激与Wnt/β-catenin信号通路研究蛇床子素对成骨细胞增殖与分化的影响及机制[D].南京中医药大学,2017.
[25] 李玲慧,丁道芳,杜国庆,等.蛇床子素对新生大鼠成骨细胞增殖的影响及相关机制研究[J].中国骨伤, 2013, 26(5):419-422.
[26] 郭英,李佩芳,舒晓春,等.骨碎补总黄酮对骨髓间充质干细胞成骨分化过程中 Wnt/β-catenin 信号通路的影响[J].中华医学杂志, 2012, 92 (32):2288-2291.
[27] Ma X,Lv J,Sun X,et al.Naringin ameliorates bone loss induced by sciatic neurectomy and increases Semaphorin 3Aexpression in denervated bone[J].Sci Rep, 2016,6: 24562.
[28] Lv J,Sun X,Ma J,et al.Involvement of periostin-sclerostin-Wnt /β-catenin signaling pathway in the prevention of neurectomy-induced bone loss by naringin[J].Biochem Biophys Res Commun, 2015,468 (4):587-593.
[29] Wang D,Ma W,Wang F,et al.Stimulation of Wnt/β-Catenin Signaling to Improve Bone Development by Naringin via Interacting with AMPK and Akt[J].Cell Physiol Biochem, 2015, 36(4):1563-1576.
[30] 陈云刚,谭国庆,任维龙,等.骨碎补含药血清经wnt/β-catenin信号通路对大鼠骨髓间充质干细胞成骨分化的影响[J].中国药理学通报, 2017, 33(6):830-836.
[31] 洪郭驹,陈鹏,韩晓蕊,等.复方贞术调脂胶囊调控MEKK2-Wnt偶联拮抗β-catenin泛素化改善大鼠糖皮质激素骨质疏松症[J].中国实验动物学报, 2018, 26(1):36-44.
[32] 沈霖,马陈,帅波,等.青娥丸对绝经后骨质疏松症患者β-catenin和DKK-1表达水平的影响[J].中西医结合研究, 2016, 8(6):281-284.
[33] 杨军,莫新民.壮骨止痛方对骨质疏松大鼠Wnt/β-catenin信号通路、血清Sclerostin水平的影响[J].中医药通报, 2017, 16(3):67-69.
[34] 马苟平.基于经典Wnt-β-catenin通路六味地黄丸抗去势大鼠骨质疏松作用的机制研究[D].浙江中医药大学, 2015.
[35] 李建国,谢兴文,李宁,等.中医非药物治疗原发性骨质疏松症的临床研究概况[J].中国骨质疏松杂志,2018,24(9):1250-1254.
[36] 刘海龙,卫荣.绝经后骨质疏松症中西医临床治疗进展[J].现代中西医结合杂志, 2014, 23(14):1594-1596.
[37] Tohda C, Nagata A. Epimedium koreanum Extract and Its Constituent Icariin Improve Motor Dysfunction in Spinal Cord Injury[J].Evidence-based Complementary and Alternative Medicine, 2012, 7(9):1208.
[38] 李翠娟,巩振东,崔馨文,等.Wnt信号通路与骨质疏松症发病关系及中医药治疗研究进展[J].现代中医药, 2016, 36(2):97-100.
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