卢非凡;张启栋;王卫国;郭万首;

• 1:北京大学中日友好临床医学院
• 2:中日友好医院

摘要(Abstract)：

股骨头坏死是我国骨科的常见病和难治性疾病,近年来对激素性股骨头坏死的研究进展迅速。糖皮质激素的大量使用是导致股骨头坏死发生的重要原因之一,但是糖皮质激素导致股骨头坏死的具体机制尚未完全阐明。目前研究发现有许多信号通路与股骨头坏死的发生有着密切联系,包括TGF-β/Smad,Wnt/β-catenin,PI3k/Akt,TLR4,PPARγ,TNF-α-STAT1-Caspase-3等多条信号通路。这些信号通路通过促进骨细胞与成骨细胞的凋亡,促进骨髓间充质干细胞脂肪化,破坏成骨细胞与破骨细胞之间的平衡,影响股骨头血供等多方面参与股骨头坏死的发生和发展。本文综述股骨头坏死发生的信号通路与股骨头坏死之间的关系,为股骨头坏死进行预防和早期诊治提供帮助。

关键词(KeyWords)： 股骨头坏死;信号通路;糖皮质激素;TGF-β/Smad;Wnt/β-catenin

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(编号:81273972、81673776)

作者(Author): 卢非凡;张启栋;王卫国;郭万首;

Email:

DOI:

参考文献(References)：

• [1]Guo S,Mao L,Ji F,et al.Activating AMP-activated protein kinase by anα1 selective activator compound 13 attenuates dexamethasone-induced osteoblast cell death[J].Biochem Biophysical Res Comm,2016,471(4):545-552.
• [2]Zhang C,Zou Y,Ma J,et al.Apoptosis associated with Wnt/β-catenin pathway leads to steroid-induced avascular necrosis of femoral head[J].BMC Musculoskeletal Disorders,2015,1.
• [3]Ding H,Wang T,Xu D,et al.Dexamethasone-induced apoptosis of osteocytic and osteoblastic cells is mediated by TAK1 activation[J].Biochem Biophysical Res Comm,2015,460(2):157-163.
• [4]Rahman MS,Akhtar N,Jamil HM,et al.TGF-beta/BMP signaling and other molecular events:regulation of osteoblastogenesis and bone formation[J].Bone Res,2015,(1):15005.
• [5]Yan Yang HN.Effects of the combined herba epimedii and fructus ligustri lucidi on bone turnover and TGF/Smads pathway in GIOP rats[J].J Ethnopharmacol,2017,201(1):91-99.
• [6]Zhu Z,Zhang C,Song W.Rational derivation,extension,and cyclization of self-inhibitory peptides to target TGF-β/BMP signaling in ONFH[J].Amino Acids,2017,49(2):283-290.
• [7]Zhang Y,Yin J,Ding H,et al.Vitamin K2 ameliorates damage of blood vessels by glucocorticoid:a potential mechanism for its protective effects in glucocorticoid-induced osteonecrosis of the femoral head in a rat model[J].Int J Biological Sci,2016,7:776-785.
• [8]Xie J,Tu T,Zhou S,et al.Transforming growth factor(TGF)-β1signal pathway:a promising therapeutic target for attenuating cardiac fibrosis[J].Int J Cardiology,2017:9.PMID:28560990.
• [9]Wu X,Zhang Y,Guo X,et al.Identification of differentially expressed micro RNAs involved in non-traumatic osteonecrosis through micro RNA expression profiling[J].Gene,2015,56(1):22-29.
• [10]Han N,Li Z,Cai Z,et al.P-glycoprotein overexpression in bone marrow-derived multipotent stromal cells decreases the risk of steroid-induced osteonecrosis in the femoral head[J].J Cellular Molecular Med,2016,11:2173-2182.
• [11]Kim S,Williams DW,Lee C,et al.IL-36 induces bisphosphonaterelated osteonecrosis of the jaw-like lesions in mice by inhibiting TGF-β-mediated collagen expression[J].J Bone Mineral Res,2017,32(2):309-318.
• [12]Yu W,Zhu C,Xu W,et al.Neuropeptide Y1 receptor regulates glucocorticoid-induced inhibition of osteoblast differentiation in murine MC3T3-E1 cells via ERK sgnaling[J].Int J Molecular Sci,2016,10(12):2150.
• [13]Liu G,Luo G,Bo Z,et al.Impaired osteogenic differentiation associated with connexin43/micro RNA-206 in steroid-induced avascular necrosis of the femoral head[J].Exper Molecular Pathol,2016,101(1):89-99.
• [14]Jia J,Feng X,Xu W,et al.Mi R-17-5p modulates osteoblastic differentiation and cell proliferation by targeting SMAD7 in non-traumatic osteonecrosis[J].Exper Molecular Med,2014,46(46):107.
• [15]Wang XL,Wang N,Zheng LZ,et al.Phytoestrogenic molecule desmethylicaritin suppressed adipogenesis via Wnt/beta-catenin signaling pathway[J].Eur J Pharmacol,2013,714(1-3):254-260.
• [16]Chen Y,Tao S,Xu Z,et al.Novel Akt activator SC-79 is a potential treatment for alcohol-induced osteonecrosis of the femoral head[J].Oncotarget,2017,8(19):31065-31078.
• [17]Piovan E,Yu J,Tosello V,et al.Direct reversal of glucocorticoidresistance by AKT inhibition in acute lymphoblastic leukemia[J].Cancer Cell,2013,24(6):766-776.
• [18]Zou W,Yang S,Zhang T,et al.Hypoxia enhances glucocorticoidinduced apoptosis and cell cycle arrest via the PI3K/Akt signaling pathway in osteoblastic cells[J].J Bone Mineral Metabolism,2015,33(6):615-624.
• [19]Liu X,Li Q,Niu X,et al.Exosomes secreted from human-induced pluripotent stem cell-derived mesenchymal stem cells prevent osteonecrosis of the femoral head by promoting angiogenesis[J].Int J Biological Sci,2017,13(2):232-244.
• [20]Tian L,Zhou DS,Wang KZ,et al.Association of toll-like receptor4 signaling pathway with steroid-induced femoral head osteonecrosis in rats[J].J Huazhong Univ Sci Technolog Med Sci,2014,34(5):679-686.
• [21]Adapala NS,Yamaguchi R,Phipps M,et al.Necrotic bone stimulates proinflammatory responses in macrophages through the activation of toll-like receptor 4[J].Am J Pathol,2016,186(11):2987-2999.
• [22]Tian L,Wen Q,Dang X,et al.Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis[J].BMC Musculoskeletal Dis,2014,15(1):1-12.
• [23]Okazaki S,Nagoya S,Matsumoto H,et al.TLR4 stimulation and corticosteroid interactively induce osteonecrosis of the femoral head in rat[J].J Orthop Res,2016,34(2):342-345.
• [24]Wang T,Teng S,Zhang Y,et al.Role of mesenchymal stem cells on differentiation in steroid-induced avascular necrosis of the femoral head[J].Exp Therapeutic Med,2017,13(2):669-675.
• [25]Jin H,Xu T,Chen Q,et al.The fate and distribution of autologous bone marrow mesenchymal stem cells with intra-arterial infusion in osteonecrosis of the femoral head in dogs[J].Stem Cells Int,2016,9(1):1-10.
• [26]Fu Q,Tang N,Zhang Q,et al.Preclinical study of cell therapy for osteonecrosis of the femoral head with allogenic peripheral bloodderived mesenchymal stem cells[J].Yonsei Med J,2016,57(4):1006.
• [27]Li J,Li Y,Wang Y,et al.Preventive effects of si RNA targeting PPARγgene on steroid-induced osteonecrosis in rabbits[J].Connective Tissue Res,2014,55(6):322-330.
• [28]Gu C,Xu Y,Zhang S,et al.mi R-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARgamma and GREM1[J].Sci Rep,2016,6:38491.
• [29]Song Y,Du Z,Ren M,et al.Association of gene variants of transcription factors PPARγ,RUNX2,Osterix genes and COL2A1,IGFBP3 genes with the development of osteonecrosis of the femoral head in Chinese population[J].Bone,2017,101:104-112.
• [30]Jiang Y,Lin WCAN.Pravastatin prevents steroid-induced osteonecrosis in rats by suppressing PPARc expression and activating Wnt signaling pathway[J].Experimental Biology Med,2014,239(3):347-355.
• [31]Kong X,Li X,Zhang C,et al.Ethyl acetate fraction of Huogu formula inhibits adipogenic differentiation of bone marrow stromal cells via the BMP and Wnt signaling pathways[J].Int J Biological Sci,2017,13(4):480-491.
• [32]Li S,Wang J.Salvianolic acid B prevents steroid-induced osteonecrosis of the femoral head via PPARγexpression in rats[J].Exp Therapeutic Med,2017,13(2):651-656.
• [33]Wu X,Feng X,He Y,et al.IL-4 administration exerts preventive effects via suppression of underlying inflammation and TNF-β-induced apoptosis in steroid-induced osteonecrosis[J].Osteoporosis Int,2016,27(5):1827-1837.