骨关节炎软骨退变与炎症的关系.doc

MAPKWnt/β-catenin ;(osteoarthritisOA)(ECM)-OA(MMPs)OA1 OAOAOA-1(IL-1)MMPs1OA2OAECM32 OAOAOA4OAECMMMPs5ECMOA3 6OA7(MAPK)(NF-κB)Wnt/β-catenin3.1 MAPK MAPK/MAPK(ERK)c-Jun N(JNK)/(SAPK)p38 MAPKERK5/BMK14p38 MAPKp38 MAPKECMMMPs8p38 MAPKp38 MAPK22CCEBPp38 MAPK92NF-κB12Cc-Junc-Jun18IL-1-α(TNF-α)MMPsIL-1p38 MAPK10TNF-α11TNF-αIL-1MMPsECMOATNF-αp38 MAPKp38 MAPKTNF-α12TNF-αJNKBcl-2Mcl-1133.2 NF-κB NF-κBNF-κBIκBIκB(IKK)NF-κB14NF-κBIKKIKKIκBIκB15IκBNF-κBNF-κBNF-κBNF-κB16NF-κBECMNF-κBMMPs17TNF-αIL-1NF-κBNF-κBTNF-αIL-1MMP-1MMP-3MMP-1318-20OA4 ECMECMOA2627OAMMPs10(MMP-1813)(MMP-371011)(MMP-29)28MMPECMOAMMP-123791329-30MMPs(TIMPs)MMPs31IL-1TNF-αMAPKsNF-κBE2MMPsMMPsMMPsECM5 OAOAOAOA1 Lijima HAoyama TIto Aet al.Destabilization of the medial meniscus leads to subchondral bone defects and site-specific cartilage degeneration in an experimental rat modelJ.Osteoarthritis Cartilage201422(7)1036-1043.2 Mobasheri AKalameqam GMusumeci Get al.Chondrocyte and mesenchymal stem cell-based therapies for cartilage repair in osteoarthritis and related orthopaedic conditionsJ.Maturitas201478(3)188-198.3 Li GYin JGao Jet al.Subchondral bone in osteoarthritisinsighe into risk factors and microstructural changesJ.Arthritis Res Ther201315(6)223.4 Martín-Millán MCasta?eda S.Estrogensosteoarthritis and inflammationJ.Joint Bone Spine201380(4)368-373.5 .J.201115(20)3763-3766.6 Smeriqlio PDhulipala LLai JHet al.Collagen VI Enhances Cartilage Tissue Generation by Stimulating Chondrocyte ProliferationJ.Tissue Enq Part A201521(3-4)840-849.7 .MAPKJ.201427(5)441-444.8 .p38 MAPKJ.201132(6)343-345.9 Obata TBrown GEYaffe MB.MAP kinase pathways activated by stressthe p38 MAPK pathwayJ.Crit Care Med200028(4)67-77.10 .MAPKJ.20111(8)32-34.11 .MMP-9J.20126(10)2614-2617.12 Kimura HMikami DKamjyama Ket al.Telmisartana possible PPAR-δ agonist reduces TNF-α-stimulated VEGF C production by inhibiting the p38 MAPK/HSP 27 pathway in human proximal renal tubular cellJ.Biochem Biophys Res Commun2014454(2)320-327.13 .p38 MAPKJ.201344(1)62-64.14 Hayden MSGhosh S.Shared principles in NF-κB signalingJ.Cell2008132(3)344-362.15 Rigoglou SPapavassiliou AG.The NF-κB signalling pathway in osteoarthritisJ.Int J Biochem Cell Biol201345(11)2580-2584.16 Forsyth CBCole AMurphy Get al.Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuliJ.J Gerontol A Biol Sci Med Sci200560(9)1118-1124.17 Buhrmann CShayan PAggarwal BBet al.Evidence that TNF-β(lymphotoxin α)can activate the inflammatory environment in human chondrocytesJ.Arthritis Res Ther201315(6)R202.18 .NF-κBJ.201218(1)78-82.19 Sondergaard BCSchultz NMadsen SHet al.MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation-divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradationJ.Osteoarthritis Cartilage201018(3)279-288.20 Lu YCJayakumar TDuann YFet al.Chondroprotective role of sesamol by inhibiting MMPs expression via retaining NF-KB signaling in activated SWl353 cellJ.J Agric Food Chem201159(9)4969-4978.21 Takeda KAkira S.Toll-like receptors in innate immunityJ.Int Immunol200517(1)1-14.22 .WntJ.201133(2)103-111.23 .Wnt/β-cateninJ.201326(7)613-616.25 .WntJ.201025(4)320-323.26 Hoff PButtgereit FBurmester GRet al.Osteoarthritis synovial fluid activates pro-inflammatory cytokines in primary human chondrocytesJ.Int Orthop201337(1)145-151.27 Lahm AMrosek ESpank Het al.Changes in content and synthesis of collagen types and proteoglycans in osteoarthritis of the knee joint and comparison of quantitative analysis with photoshop-based imageanalysisJ.Arch Orthop Trauma Surg2010130(4)557-564.28 Garqiulo SGamba PPoli Get al.Metalloproteinases and metallopr-oteinase in-hibitors in age-related diseasesJ.Curr Pharm Des201420(18)2993-3018.29 Fujita YShiomi TYanagimoto Set al.Tetraspanin CD151 is expressed in osteoarthritic cartilage and is involved in pericellular activation of pro-matrix metalloproteinase7 in osteoarthritic chondrocytesJ.Arthritis