邓立庆;谭振;康鹏德;

• 1:四川大学华西临床医学院/华西医院骨科(关节外科)

摘要(Abstract)：

<正>锂盐作为精神科用药被广泛应用,最初认为锂盐治疗后可能伴有甲状旁腺功能亢进,可增加患者骨质疏松症的危险;但锂盐可独立影响骨代谢,并增加骨密度[1]。最近研究表明,锂盐通过抑制GSK-3β激活Wnt信号通路而促进成骨[2~5]。间充质干细胞(mesenchymal stem cells,MSCs)是近年来发现的一类具有多向分化潜能的成体干细胞,主要存在于骨髓,

关键词(KeyWords)： 锂盐;间充质干细胞;Wnt信号通路;成骨分化;骨形成

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金面上项目(编号:81271976/H0605、81171763和30772202/C1607);; 四川省科技支撑计划项目资助(编号:2011SZ0027)

作者(Author): 邓立庆;谭振;康鹏德;

Email:

DOI:

参考文献(References)：

• [1]Zamani A,Omrani GR,Nasab MM,et al.Lithium’s effect on bone mineral density[J].Bone,2009:331-334.
• [2]Zhu Z,Kremer P,Tadmori I,et al.Lithium suppresses astrogliogenesis by neural stem and progenitor cells by inhibiting STAT3 pathway independently of glycogen synthase kinase 3 beta[J].PLoS One,2011,9:233-241.
• [3]Li F,He Z,Li Y,et al.Combined activin A/LiCl/Noggin treatment improves production of mouse embryonic stem cell-derived definitive endoderm cells[J].J Cell Biochem,2011,4:1022-1034.
• [4]Nakatsu MN,Ding Z,Ng MY,et al.Wnt/β-catenin signaling regulates proliferation of human cornea epithelial stem/progenitor cells[J].Invest Ophthalmol Vis Sci,2011,7:4734-4741.
• [5]Li J,Khavandgar Z,Lin SH,et al.Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3-independent mechanism[J].Bone,2011,2:321-331.
• [6]Pittenger MF,Mackay AM,Beck SC,et al.Muhilineage potential of adult human mesenchymal stem cells[J].Science,1999,5411:143-147.
• [7]Hong JH,Hwang ES,McManus MT,et al.TAZ,a transcriptional modulator of mesenehymal stem cell differentiation[J].Science,2005,5737:1074-1078.
• [8]Jadlowiec J,Koch H,Zhang X,et al.Phosphophoryn regulates the gene expression and differentiation of NIH3T3,MC3T3-E1,and human mesenchymal stem cells via the integrin/MAPK signaling pathway[J].J Biol Chem,2004,51:53323-53330.
• [9]Boland GM,Perkins G,Hall DJ,et al.Wnt 3a promotes proliferation and suppresses osteogenic differentiation of adult human mesenchymal stem cells[J].J Cell Biochem,2004,6:1210-1230.
• [10]Qiu W,Chen L,Kassem M.Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with differentiation fate determination of human bone marrow stromal(mesenchymal)stem cells[J].Biochem Biophys Res Commun,2011,1:98-104.
• [11]Wagner ER,Zhu G,Zhang BQ,et al.The therapeutic potential of the Wnt signaling pathway in bone disorders[J].Curt Mol Pharmacol,2011,1:14-25.
• [12]Baron R,Rawadi G.Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton[J].Endocrinology,2007,6:2635-2643.
• [13]MacDonald BT,Tamai K,He X.Wnt/β-catenin signaling:components,mechanisms,and diseases[J].Dev Cell,2009,1:9-26.
• [14]Maurice Kle'ber and Lukas Sommer.Wnt signaling and the regulation of stem cell function[J].Curr Opin Cell Biol,2004,16:681-687.
• [15]Etheridge SL,Spencer GJ,Heath DJ,et al.Expression profiling and functional analysis of wnt signaling mechanisms in mesenchymal stem cells[J].Stem Cells,2004,5:849-860.
• [16]Willert K,Brown JD,Danenberg E,et al.Wnt proteins are lipidmodified and Can act as stem cell growth factors[J].Nature,2003,6938:448-452.
• [17]Frances M,Kong WN.Is Wnt signalling the final common pathway leading to bone formation[J].Mol Cell Endocrinol,2009,1/2:52-62.
• [18]Baron R,Rawadi G.Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton[J].Endocrinology,2007,6:2635-2643.
• [19]Verkaar F,Zaman GJ.New avenues to target Wnt/β-catenin signaling[J].Drug Discov Today,2011,1-2:35-41.
• [20]Holmen SL,Giambernardi TA,Zylstra CR,et al.Decreased BMD and limd deformities in mice carrying mutations in both lrp5 and lrp6[J].J Bone Miner Res,2004,12:2033-2040.
• [21]Kato M,Patel MS,Levasseur R,et al.Cbfal-independent decrease in osteoblast proliferation,osteopenia,and persistent embryonic eye vascularization in mice deficiet in lrp5,Wnt coreceptor[J].J Cell Biol,2002,2:303-314.
• [22]Fujino T,Asaba H,Kang MJ,et al.Low-density lipoprotein recoptor-rdated protein 5(LRP5)is essential for normal cholesterol metabolism and glucose-induced insulin secretion[J].Proc Natl Acad Sci USA,2003,1:229-234.
• [23]Little RD,Carulli JP,Del Mastro RG,et al.A mutation in the LDL receptorrealated protein 5 gene results in the autosomal dominant high-bone-mass trait[J].Am J Hum Genet,2002,1:11-19.
• [24]Van Wesenbeeck L,Cleiren E,Gram J,et al.Six novel miasense mutations in the LDL receptorrelated protein 5(LRP5)gene in different conditions with an increased bone density[J].Am J Hum Genet,2003,3:763-771.
• [25]Bennett CN,Longo KA,Wright WS,et al.Regulation of osteoblastogenesis and bone mass by WntlOb[J].Proc Natl Acad Sci USA,2005,9:3324-3329.
• [26]Bobij P,Zhao W,Small C,et al.High bone mass in mice expressing a mutant LRP5 gene[J].J Bone Miner Res,2003,6:960-974.
• [27]Yu HM,Jercbow B,Sheu TJ,et al.The role of Axin2 in calvarial morphogenesis and craniosynostosis[J].Development,2005,8:1995-2005.
• [28]Vacheron-Trystrarn MN,Bmitman A,Cheref S,et al.Antipsychotics in bipolar disorders[J].Encephale,2004,5:417-424.
• [29]Yang Y,Yang J,Liu R,et al.Accumulation ofβ-catenin by lithium chloride in porcine myoblast cultures accelerates cell differentiation[J].Mol Biol Rep,2011,3:2043-2049.
• [30]Young W.Review of lithium effects on brain and blood[J].Cell Transplantation,2009,18:951-975.
• [31]Struewing I,Boyechko T,Barnett C,et al.The balance of TCF7L2variants with differential activities in Wnt-signaling is regulated by lithium in a GSK3beta-independent manner[J].Biochem Biophys Res Commun,2010,2:245-250.
• [32]Silva AK,Yi H,Hayes SH,et al.Lithium chloride regulates the proliferation of stem-like cells in retinoblastoma cell lines:a potential role for the canonical Wnt signaling pathway[J].Mol Vis,2010,16:36-45.
• [33]Cong Y,Slee RB,Fukai N,et al.LDL receptor-related protein 5(LRP5)bone accrual and eye development[J].Cell,2001,4:513-523.
• [34]Ohnaka K,Taniguchi H,Kawte H,et al.Glucocorticoid enhances the expression of dickkopf-1 in human osteoblasts:novel mechanism of glucocorticoid-induced osteoporosis[J].Biochem Biophys Res Commum,2004,1:259-264.
• [35]Ohnaka K,Tanabe M,Kawte H,et al.Glucocorticoid suppresses the canonica Wnt signal in cultured human osteoblasts[J].Biochem Biophys Res Commum,2005,1:177-181.
• [36]Wang FS,Lin CL,Chenm YJ,et al.Secreted frizzled-related protein1 modulates glucocorticoid attenuation of osteogenic activities and bone mass[J].Endocrinology,2005,5:2415-2423.
• [37]Li HX,Luo X,Liu BX,et al.Roles of Wnt/beta-catenin signaling in adipogenic differentiation potential of adipose-derived mescnchymal stem cells[J].Mol Cell Endocrinol,2008,1-2:116-124.
• [38]Claire ME,James RE,Seint TL,et al.Increasing Wnt signaling in the bone marrow microenvironment inhibits the development of myeloma bone disease and reduces tumor burden in bone in vivo[J].Blood,2008,5:2833-2842.
• [39]Chen Y,Whetstone HC,Lin AC,et al.Beta-catenin signaling plays a disparate role in different phases of fracture repair:implications for therapy to improve bone healing[J].PLoS Med,2007,7:249.
• [40]Vestergaard P,Rejnmark L,Mosekilde L.Reduced relative risk of fractures among users of lithium[J].Calcif Tissue Int,2005,1:1-8.
• [41]Clement-Laeroix P,Ai M,Morvan F,et al.Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice[J].Proc NatlAcad Sci USA,2005,48:17406-17411.
• [42]Khorami M,Hesaraki S.In vitro bioactivity and biocompatibility of lithium substituted 45s5 bioglass[J].Mat Sci Eng C,2011,31:1584-1592.