中药诱导骨髓间充质干细胞成软骨及成骨分化的研究进展
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摘要
骨髓间充质干细胞(BMSCs)不仅具有强大的自我更新能力、多向分化潜能,还兼具低免疫原性及归巢能力,是骨及软骨组织工程中理想的种子细胞。目前,诱导BMSCs分化的细胞因子由于价格昂贵和安全性问题而无法广泛应用于临床实践中。研究表明中药及其有效成分可诱导BMSCs分化,具有与细胞因子类似的生理活性。文章旨在对中药诱导BMSCs成软骨及成骨分化的研究进展进行综述,以期为骨科疾病的防治研究提供参考。
Bone marrow mesenchymal stem cells(BMSCs) are characterized by strong self-renewal ability, multi-directional differentiation potential, low immunogenicity and good-homing ability. Thus, BMSCs are ideal seed cell for bone and cartilage tissue engineering. At present, BMSCs differentiation induced by cytokines cannot be widely applied in clinical practice due to the expensiveness and safety issues. Recent studies have shown that Chinese materia medica and its active ingredients can induce the differentiation of BMSCs, and have similar physiological activity as cytokines. In this paper, we aimed to review the research advances of BMSCs chondrogenesis and osteogenesis induced by Chinese materia medica, and to provide references for the prevention and/or treatment of orthopedic diseases.
Bone marrow mesenchymal stem cells(BMSCs) are characterized by strong self-renewal ability, multi-directional differentiation potential, low immunogenicity and good-homing ability. Thus, BMSCs are ideal seed cell for bone and cartilage tissue engineering. At present, BMSCs differentiation induced by cytokines cannot be widely applied in clinical practice due to the expensiveness and safety issues. Recent studies have shown that Chinese materia medica and its active ingredients can induce the differentiation of BMSCs, and have similar physiological activity as cytokines. In this paper, we aimed to review the research advances of BMSCs chondrogenesis and osteogenesis induced by Chinese materia medica, and to provide references for the prevention and/or treatment of orthopedic diseases.
引文
[1]Chen J,Liu G,Weng X,et al.Tougu Xiaotong formula induces chondrogenic differentiation in association with transforming growth factor-β1 and promotes proliferation in bone marrow stromal cells[J].International journal of molecular medicine,2015,35(3):747-754.
[2]陈祁青,金红婷,应俊,等.右归饮含药血清对骨髓间充质干细胞成软骨分化的促进作用及其micro RNA表达谱分析[J].中华中医药杂志,2015,30(5):1380-1386.
[3]吴追乐,刘献祥,李西海,等.透骨消痛颗粒诱导骨髓间充质干细胞向软骨细胞的分化[J].中国组织工程研究与临床康复,2009,13(33):6456-6460.
[4]李楠,王和鸣,李文顺,等.龟鹿二仙胶汤含药血清对兔体外BMSCs向软骨细胞分化的干预作用[J].上海中医药大学学报,2007,21(6):58-61.
[5]马笃军,彭力平,王立新,等.牛膝醇提物诱导兔骨髓间充质干细胞软骨定向分化的实验研究[J].中国中医骨伤科杂志,2017,25(2):6-11.
[6]钱晓伟,潘丹岷,谭湘陵,等.中药血清对大鼠BMSCs体外成软骨分化中Col2a1和Acan表达的影响[J].时珍国医国药,2012,23(2):340-343.
[7]高明珠.熟地水提液、骨碎补水提取液诱导大鼠BMSCs向软骨分化的实验研究[J].中国临床康复杂志,2006,9(34):45-46.
[8]Lu Z,Lei D,Jiang T,et al.Nerve growth factor from Chinese cobra venom stimulates chondrogenic differentiation of mesenchymal stem cells[J].Cell death&disease,2017,8(5):e2801.
[9]王冠军.柚皮苷对大鼠BMSCs增殖及成软骨分化的影响[D].暨南大学,2009.
[10]肖军,马德彰,杨钟华,等.淫羊藿苷促进入骨髓间充质干细胞成软骨分化的研究[J].中华实验外科杂志,2013,30(7):1357-1359.
[11]Wang ZC,Sun HJ,Li KH,et al.Icariin promotes directed chondrogenic differentiation of bone marrow mesenchymal stem cells but not hypertrophy in vitro[J].Experimental and therapeutic medicine,2014,8(5):1528-1534.
[12]汪建样,殷嫦嫦,武翠翠,等.淫羊藿素通过Wnt/β-catenin信号通路促进BMSCs成软骨分化[J].中国中药杂志,2016,41(4):694-699.
[13]嵇玲瑛.部位、年龄对h BMSCs活性的影响及倍半菇促h BMScs成软骨分化的临床实验研究[D].广州:广州中医药大学,2011.
[14]吴险峰,尚希福,胡飞.茶黄素和转化生长因子β-1对兔骨髓间充质干细胞向软骨细胞增殖及诱导分化的影响[J].中国组织工程研究与临床康复,2009,13(14):2717-2721.
[15]修忠标,林建华,吴朝阳,等.鹿茸多肽对兔骨髓间质干细胞体外软骨表型诱导分化的影响[J].中国骨伤,2007,20(1):31-33.
[16]梁祖建,吴春飞,张百挡.补肾调肝方诱导衰老BMSCs成骨分化的实验研究[J].中国骨质疏松杂志,2013,19(3):212-216.
[17]Wen-hai Z,Xiu-lan L,Yang Z,et al.Effect of Sheng-Ji liquor on in vitro osteogenesis of bone marrow-derived mesenchymal stem cells in rabbits[J].Journal of Clinical Rehabilitative Tissue Engineering Research,2007,11(37):7489-7493.
[18]龚建文.从P38信号通路探讨中药骨康方对去势大鼠MSCs成骨分化的机制研究[D].广州:广州中医药大学,2011.
[19]刘光旺,高娟,郭含军,等.补肾填精中药血清对去势小鼠骨髓干细胞Wnt/β-catenin成骨分化信号通路的影响[J].中国骨质疏松杂志,2013,19(4):324-329.
[20]徐凌霄,高俊,张前德.左归丸含药血清对大鼠骨髓间充质干细胞骨向分化中碱性磷酸酶含量的影响[J].中国实验方剂学杂志,2011,17(7):149-152.
[21]杨锋,潘乐,马秋涛,等.左归丸对骨髓间充质干细胞成骨分化相关基因甲基化的影响[J].中医杂志,2015,56(15):1326-1329.
[22]Shuai B,Shen L,Zhu R,et al.Effect of Qing'e formula on the in vitro differentiation of bone marrow-derived mesenchymal stem cells from proximal femurs of postmenopausal osteoporotic mice.[J].Bmc Complementary&Alternative Medicine,2015,15(1):250.
[23]李丹青,肖强兵,巴戟天多糖通过p38 MAPK信号通路促间充质干细胞成骨分化的体外研究[J].中国中医骨伤科杂志,2015,23(5):1-4,8.
[24]Jiang Y,Zhang Y,Chen W,et al.Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling.[J].Journal of Translational Medicine,2014,12(1):334.
[25]Yang S,Zhou Y,Shuai B,et al.Role of the ER/NO/c GMP Signaling Pathway in the Promotion of Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Actaea racemosa Extract[J].Evidence-Based Complementray and Alternative Medicine,2016(44):1-10.
[26]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.
[27]Zong S,Zeng G,Zou B,et al.Effects of Polygonatum sibiricum polysaccharide on the osteogenic differentiation of bone mesenchymal stem cells in mice[J].International Journal of Clinical&Experimental Pathology,2015,8(6):6169-6180.
[28]Yang F,Yuan P,Hao Y Q,et al.Emodin enhances osteogenesis and inhibits adipogenesis[J].Bmc Complementary&Alternative Medicine,2014,14(1):74.
[29]Ming L,Ge B,Chen K,et al.Effects of isopsoralen on bone marrow stromal stem cells differentiate and proliferate in vitro[J].China Journal of Chinese Materia Medica,2011,36(15):2124-2128.
[30]廖清船,肖洲生,秦艳芳,等.植物雌激素金雀异黄酮通过p38MAPK通路促进骨髓间充质干细胞向成骨细胞分化[J].中国药理学通报,2006,22(6):683-687.
[31]Zhang JF,Li G,Chan CY,et al.Flavonoids of Herba Epimedii regulate osteogenesis of human mesenchymal stem cells through BMP and Wnt/beta-catenin signaling pathway[J].Molecular&Cellular Endocrinology,2010,314(1):70-74.
[32]Yin XX,Chen ZQ,Liu Z J,et al.Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2[J].中华医学杂志(英文版),2007,120(3):204-210.
[33]鲍远,黄俊明,靖兴志,等.淫羊藿苷促进骨髓间充质干细胞成骨分化[J].中国组织工程研究,2016,20(24):3501-3507.
[34]翟远坤,陈克明,葛宝丰,等.淫羊藿次苷Ⅱ通过激活雌激素信号通路促进骨髓间充质干细胞的成骨性分化[J].中国药理学通报,2011,27(10):1451-1457.
[35]Yang LI,Wang J,Chen G,et al.Quercetin promotes the osteogenic differentiation of rat mesenchymal stem cells via mitogen-activated protein kinase signaling[J].Experimental&Therapeutic Medicine,2015,9(6):2072-2080.
[36]Zhou Y,Wu Y,Jiang X,et al.The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells[J].Plos One,2015,10(6):e0129605.
[37]Zhang,Aiguo,et al.Resveratrol rescued the TNF-α-induced impairments of osteogenesis of bone-marrow derived mesenchymal stem cells and inhibited the TNF-α-activated NF-кB signaling pathway[J].International Immunopharmacology,2015,(26):409-415.
[2]陈祁青,金红婷,应俊,等.右归饮含药血清对骨髓间充质干细胞成软骨分化的促进作用及其micro RNA表达谱分析[J].中华中医药杂志,2015,30(5):1380-1386.
[3]吴追乐,刘献祥,李西海,等.透骨消痛颗粒诱导骨髓间充质干细胞向软骨细胞的分化[J].中国组织工程研究与临床康复,2009,13(33):6456-6460.
[4]李楠,王和鸣,李文顺,等.龟鹿二仙胶汤含药血清对兔体外BMSCs向软骨细胞分化的干预作用[J].上海中医药大学学报,2007,21(6):58-61.
[5]马笃军,彭力平,王立新,等.牛膝醇提物诱导兔骨髓间充质干细胞软骨定向分化的实验研究[J].中国中医骨伤科杂志,2017,25(2):6-11.
[6]钱晓伟,潘丹岷,谭湘陵,等.中药血清对大鼠BMSCs体外成软骨分化中Col2a1和Acan表达的影响[J].时珍国医国药,2012,23(2):340-343.
[7]高明珠.熟地水提液、骨碎补水提取液诱导大鼠BMSCs向软骨分化的实验研究[J].中国临床康复杂志,2006,9(34):45-46.
[8]Lu Z,Lei D,Jiang T,et al.Nerve growth factor from Chinese cobra venom stimulates chondrogenic differentiation of mesenchymal stem cells[J].Cell death&disease,2017,8(5):e2801.
[9]王冠军.柚皮苷对大鼠BMSCs增殖及成软骨分化的影响[D].暨南大学,2009.
[10]肖军,马德彰,杨钟华,等.淫羊藿苷促进入骨髓间充质干细胞成软骨分化的研究[J].中华实验外科杂志,2013,30(7):1357-1359.
[11]Wang ZC,Sun HJ,Li KH,et al.Icariin promotes directed chondrogenic differentiation of bone marrow mesenchymal stem cells but not hypertrophy in vitro[J].Experimental and therapeutic medicine,2014,8(5):1528-1534.
[12]汪建样,殷嫦嫦,武翠翠,等.淫羊藿素通过Wnt/β-catenin信号通路促进BMSCs成软骨分化[J].中国中药杂志,2016,41(4):694-699.
[13]嵇玲瑛.部位、年龄对h BMSCs活性的影响及倍半菇促h BMScs成软骨分化的临床实验研究[D].广州:广州中医药大学,2011.
[14]吴险峰,尚希福,胡飞.茶黄素和转化生长因子β-1对兔骨髓间充质干细胞向软骨细胞增殖及诱导分化的影响[J].中国组织工程研究与临床康复,2009,13(14):2717-2721.
[15]修忠标,林建华,吴朝阳,等.鹿茸多肽对兔骨髓间质干细胞体外软骨表型诱导分化的影响[J].中国骨伤,2007,20(1):31-33.
[16]梁祖建,吴春飞,张百挡.补肾调肝方诱导衰老BMSCs成骨分化的实验研究[J].中国骨质疏松杂志,2013,19(3):212-216.
[17]Wen-hai Z,Xiu-lan L,Yang Z,et al.Effect of Sheng-Ji liquor on in vitro osteogenesis of bone marrow-derived mesenchymal stem cells in rabbits[J].Journal of Clinical Rehabilitative Tissue Engineering Research,2007,11(37):7489-7493.
[18]龚建文.从P38信号通路探讨中药骨康方对去势大鼠MSCs成骨分化的机制研究[D].广州:广州中医药大学,2011.
[19]刘光旺,高娟,郭含军,等.补肾填精中药血清对去势小鼠骨髓干细胞Wnt/β-catenin成骨分化信号通路的影响[J].中国骨质疏松杂志,2013,19(4):324-329.
[20]徐凌霄,高俊,张前德.左归丸含药血清对大鼠骨髓间充质干细胞骨向分化中碱性磷酸酶含量的影响[J].中国实验方剂学杂志,2011,17(7):149-152.
[21]杨锋,潘乐,马秋涛,等.左归丸对骨髓间充质干细胞成骨分化相关基因甲基化的影响[J].中医杂志,2015,56(15):1326-1329.
[22]Shuai B,Shen L,Zhu R,et al.Effect of Qing'e formula on the in vitro differentiation of bone marrow-derived mesenchymal stem cells from proximal femurs of postmenopausal osteoporotic mice.[J].Bmc Complementary&Alternative Medicine,2015,15(1):250.
[23]李丹青,肖强兵,巴戟天多糖通过p38 MAPK信号通路促间充质干细胞成骨分化的体外研究[J].中国中医骨伤科杂志,2015,23(5):1-4,8.
[24]Jiang Y,Zhang Y,Chen W,et al.Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling.[J].Journal of Translational Medicine,2014,12(1):334.
[25]Yang S,Zhou Y,Shuai B,et al.Role of the ER/NO/c GMP Signaling Pathway in the Promotion of Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Actaea racemosa Extract[J].Evidence-Based Complementray and Alternative Medicine,2016(44):1-10.
[26]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.
[27]Zong S,Zeng G,Zou B,et al.Effects of Polygonatum sibiricum polysaccharide on the osteogenic differentiation of bone mesenchymal stem cells in mice[J].International Journal of Clinical&Experimental Pathology,2015,8(6):6169-6180.
[28]Yang F,Yuan P,Hao Y Q,et al.Emodin enhances osteogenesis and inhibits adipogenesis[J].Bmc Complementary&Alternative Medicine,2014,14(1):74.
[29]Ming L,Ge B,Chen K,et al.Effects of isopsoralen on bone marrow stromal stem cells differentiate and proliferate in vitro[J].China Journal of Chinese Materia Medica,2011,36(15):2124-2128.
[30]廖清船,肖洲生,秦艳芳,等.植物雌激素金雀异黄酮通过p38MAPK通路促进骨髓间充质干细胞向成骨细胞分化[J].中国药理学通报,2006,22(6):683-687.
[31]Zhang JF,Li G,Chan CY,et al.Flavonoids of Herba Epimedii regulate osteogenesis of human mesenchymal stem cells through BMP and Wnt/beta-catenin signaling pathway[J].Molecular&Cellular Endocrinology,2010,314(1):70-74.
[32]Yin XX,Chen ZQ,Liu Z J,et al.Icariine stimulates proliferation and differentiation of human osteoblasts by increasing production of bone morphogenetic protein 2[J].中华医学杂志(英文版),2007,120(3):204-210.
[33]鲍远,黄俊明,靖兴志,等.淫羊藿苷促进骨髓间充质干细胞成骨分化[J].中国组织工程研究,2016,20(24):3501-3507.
[34]翟远坤,陈克明,葛宝丰,等.淫羊藿次苷Ⅱ通过激活雌激素信号通路促进骨髓间充质干细胞的成骨性分化[J].中国药理学通报,2011,27(10):1451-1457.
[35]Yang LI,Wang J,Chen G,et al.Quercetin promotes the osteogenic differentiation of rat mesenchymal stem cells via mitogen-activated protein kinase signaling[J].Experimental&Therapeutic Medicine,2015,9(6):2072-2080.
[36]Zhou Y,Wu Y,Jiang X,et al.The Effect of Quercetin on the Osteogenesic Differentiation and Angiogenic Factor Expression of Bone Marrow-Derived Mesenchymal Stem Cells[J].Plos One,2015,10(6):e0129605.
[37]Zhang,Aiguo,et al.Resveratrol rescued the TNF-α-induced impairments of osteogenesis of bone-marrow derived mesenchymal stem cells and inhibited the TNF-α-activated NF-кB signaling pathway[J].International Immunopharmacology,2015,(26):409-415.