生物学标志物在骨关节炎诊断中的应用进展
|
摘要
骨关节炎是临床上常见的慢性关节疾病之一,具有起病慢、病程长等特点。传统的诊断方法难以做到早期发现、早期诊断,因此如何做到早发现、早诊断是治疗骨关节炎的关键。近年来随着分子生物学的发展,国内外学者发现大量与骨关节炎病情变化相关的生物学标志物,如Ⅱ型胶原降解产物、软骨寡聚基质蛋白、基质金属蛋白酶、炎性细胞因子、脂肪细胞因子等,并且生物学标志物应用于骨关节炎早期诊断也已有报道。由于个体之间存在较大差异,单一的生物标志物很难达到此要求,因此可能需要多种生物标志物联合检测,进而实现骨关节炎的早发现、早诊断、早治疗。
Osteoarthritis is one of common chronic joint diseases in clinical practice. It' s difficult for traditional diagnostic methods to realize early detection and diagnosis,so how to achieve early detection and early diagnosis is essential for the treatment of osteoarthritis. In recent years,with the development of molecular biology,scholars at home and abroad have found a large number of biological markers related to the changes of osteoarthritis,such as type Ⅱ collagen degradation product,cartilage oligomeric matrix protein,matrix metalloproteinase,inflammatory cytokines,adipocytokines,etc,and biomarkers for early diagnosis of osteoarthritis have also been reported. But due to individual,there are large differences,so a single biomarker is difficult to meet this requirement,so a combination of multiple biomarkers may be needed to achieve early detection,early diagnosis,and early treatment of osteoarthritis.
Osteoarthritis is one of common chronic joint diseases in clinical practice. It' s difficult for traditional diagnostic methods to realize early detection and diagnosis,so how to achieve early detection and early diagnosis is essential for the treatment of osteoarthritis. In recent years,with the development of molecular biology,scholars at home and abroad have found a large number of biological markers related to the changes of osteoarthritis,such as type Ⅱ collagen degradation product,cartilage oligomeric matrix protein,matrix metalloproteinase,inflammatory cytokines,adipocytokines,etc,and biomarkers for early diagnosis of osteoarthritis have also been reported. But due to individual,there are large differences,so a single biomarker is difficult to meet this requirement,so a combination of multiple biomarkers may be needed to achieve early detection,early diagnosis,and early treatment of osteoarthritis.
引文
[1] Mobasheri A,Rayman MP,Gualillo O,et al. The role of metabo-lism in the pathogenesis of osteoarthritis[J]. Nat Rev Rheumatol,2017,13(5):302-311.
[2] Peat G,Duncan RC,Wood LR,et al. Clinical features of symp-tomatic patellofemoral joint osteoarthritis[J]. Arthritis Res Ther,2012,14(2):R63-63.
[3] Atherton HJ,Jones OA,Malik S,et al. A comparative metabolics-tudy of NHR-49 in Caenorhabditis elegans and PPAR-alpha inthe mouse[J]. FEBS Letters,2008,582(12):1661-1666.
[4]周晓辉,常亚南,何晓亮,等.Ⅱ型胶原蛋白的结构、功能及其最新研究进展[J].河北科技大学学报,2017,38(2):202-208.
[5] Jordan MK. Urinary CTX-Ⅱand glucosyl-galactosyl-pyridinolineare associated with the presence and severity of radiographic kneeosteoarthritis in men[J]. Ann Rheum Dis,2005,65(7):871-877.
[6] Huang MJ,Zhao JY,Huang Y,et al. Meta-analysis of urinaryC-terminal telopeptide of typeⅡcollagen as a biomarker in oste-oarthritis diagnosis[J]. J Orthop Translat,2018,13:50-57.
[7] Tanishi N,Yamagiwa H,Hayami T,et al. Relationship betweenradiological knee osteoarthritis and biochemical markers of carti-lage and bone degradation(urine CTX-Ⅱand NTX-Ⅰ):theMatsudai Knee Osteoarthritis Survey[J]. J Bone Miner Metab,2009,27(5):605-612.
[8] Park YM,Kim SJ,Lee KJ,et al. Detection of CTX-Ⅱin serumand urine to diagnose osteoarthritis by using a fluoro-microbeadsguiding chip[J]. Biosens Bioelectron,2015,67:192-199.
[9] Sharif M,Kirwan J,Charni N,et al. A 5-yr longitudinal study oftype IIA collagen synthesis and total typeⅡcollagen degradationin patients with knee osteoarthritis-association with disease pro-gression[J]. Rheumatology(Oxford),2007,46(6):938-943.
[10] KalaE,Bahlous A,Bouzid K,et al. The role of typeⅡcollagenfragments and X-ray progression of knee osteoarthritis[J]. AnnBiol Clin(Paris),2014,72(6):715-721.
[11] Huang M,Zhao J,Huang Y,et al. Meta-analysis of urinary C-ter-minal telopeptide of typeⅡcollagen as a biomarker in osteoar-thritis diagnosis[J]. J Orthop Translat,2018,13:50-57.
[12] Tanishi N,Yamagiwa H,Hayami T,et al. Usefulness of urinaryCTX-Ⅱand NTX-Ⅰin evaluating radiological knee osteoarthri-tis:the Matsudai knee osteoarthritis survey[J]. J Orthop Sci,2014,19(3):429-436.
[13] Valdes AM,Meulenbelt I,Chassaing E,et al. Large scale meta-analysis of urinary C-terminal telopeptide,serum cartilage oligo-meric protein and matrix metalloprotease degraded typeⅡcolla-gen and their role in prevalence,incidence and progression ofosteoarthritis[J]. Osteoarthritis Cartilage,2014,22:683-689.
[14] van der Kraan PM,Stoop R,Meijers TH,et al. Expression of typeⅩcollagen in young and old C57BI/6 and Balb/c mice. Relationwith articular cartilage degeneration[J]. Osteoarthritis Cartilage,2001,9(2):92-100.
[15] Girkontaite I,Frischholz S,Lammi P,et al. Immunolocalization oftypeⅩcollagen in normal fetal and adult osteoarthritic cartilagewith monoclonal antibodies[J]. Matrix Biol,1996,15(4):231-238.
[16] Zheng Q,Keller B,Zhou G,et al. Localization of the cis-enhancerelement for mouse typeⅩcollagen expression in hypertrophicchondrocytes in vivo[J]. J Bone Miner Res,2009,24(6):1022-1032.
[17] Matsumoto T,Cooper GM,Gharaibeh B,et al. Cartilage repair in arat model of osteoarthritis through intraarticular transplantation ofmuscle-derived stem cells expressing bone morphogenetic protein4 and soluble flt-1[J]. Arthritis Rheum, 2009,60(5):1390-1405.
[18] Gu J,Lu Y,Li F,et al. Identification and characterization of thenovel Col10a1 regulatory mechanism during chondrocyte hyper-trophic differentiation[J]. Cell Death Dis,2014,5(10):e1469.
[19] He Y,Siebuhr AS,Brandt-Hansen NU,et al. TypeⅩcollagenlevels are elevated in serum from human osteoarthritis patientsand associated with biomarkers of cartilage degradation andinflammation[J]. BMC Musculoskelet Disord,2014,15(1):309.
[20] Gheita TA,El-Awar AH,El-Ansary MM,et al. Cartilage oligomericmatrix protein(COMP)levels in serum and synovial fluid inosteoarthritis(OA)patients:Correlation with clinical,radiologi-cal and laboratory parameters[J]. Osteoarthritis Cartilage,2015,23(2):A85-A85.
[21] Salminen H,Perala M,Lorenzo P,et al. Up-regulation of cartilageoligomeric matrix protein at the onset of articular cartilage degene-ration in a transgenic mouse model of osteoarthritis[J]. ArthritisRheum,2000,43(8):1742-1748.
[22] Sharif M,Kirwan JR,Elson CJ,et al. Suggestion of nonlinear orphasic progression of knee osteoarthritis based on measurements ofserum cartilage oligomeric matrix protein levels over five years[J].Arthritis Rheum,2004,50(8):2479-2488.
[23] Attur M,Krasnokutskysamuels S,Samuels J,et al. Prognosticbiomarkers in osteoarthritis[J]. Curr Opin Rheumatol,2013,25(1):136-144.
[24] Kaspiris A,Khaldi L,Chronopoulos E,et al. Macrophage-specificmetalloelastase(MMP-12)immunoexpression in the osteochondralunit in osteoarthritis correlates with BMI and disease severity[J].Pathophysiology,2015,22:143-151.
[25] HulejováH,BaresováV,Klézl Z,et al. Increased level of cyto-kines and matrix metalloproteinases in osteoarthritic subchondralbone[J]. Cytokine,2007,38(3):151-156.
[26] Pengas I,Eldridge S,Assiotis A,et al. MMP-3 in the peripheralserum as a biomarker of knee osteoarthritis,40 years after opentotal knee meniscectomy[J]. J Exp Orthop,2018,5(1):21.
[27] Wang W,Lian N,Li L,et al. Atf4 regulates chondrocyte prolifera-tion and differentiation during endochondral ossification by activa-ting Ihh transcription[J]. Development,2009,136(24):4143-4153.
[28] Wei F,Zhou J,Wei X,et al. Activation of Indian hedgehog pro-motes chondrocyte hypertrophy and upregulation of MMP-13 inhuman osteoarthritic cartilage[J]. Osteoarthritis Cartilage,2012,20(7):755-763.
[29] Zhou J,Wei X,Wei L. Indian Hedgehog,a critical modulator inosteoarthritis,could be a potential therapeutic target for attenua-ting cartilage degeneration disease[J]. Connect Tissue Res,2014,55(4):257-261.
[30] Zhang C,Wei X,Chen C,et al. Indian hedgehog in synovial fluid is anovel marker for early cartilage lesions in human knee joint[J]. Int JMol Sci,2014,15(5):7250-7265.
[31] Ozaki E,Campbell M,Doyle SL. Targeting the NLRP3 inflamma-some in chronic inflammatory diseases:Current perspectives[J].J Inflamm Res,2015,8:15-27.
[32] Mc Allister MJ,Chemaly M,Eakin AJ,et al. NLRP3 as a poten-tially novel biomarker for the management of osteoarthritis[J].Osteoarthritis Cartilage,2018,26(5):612-619.
[33] Clavijo-Cornejo D,Martínez-Flores K,Silva-Luna K,et al. TheOverexpression of NALP3 Inflammasome in Knee Osteoarthritis IsAssociated with Synovial Membrane Prolidase and NADPH Oxi-dase 2[J]. Oxid Med Cell Longev,2016,2016:1472567.
[34] Jin C,Frayssinet P,Pelker R,et al. NLRP3 inflammasome plays acritical role in the pathogenesis of hydroxyapatite-associatedarthropathy[J]. Proc Natl Acad Sci U S A,2011,108(36):14867-14872.
[35] Scanzello CR,Goldring SR. The role of synovitis in osteoarthritispathogenesis[J]. Bone,2012,51(2):249-257.
[36] Johansen JS,Jensen HS,Price PA. A new biochemical marker forjoint injury. Analysis of YKL-40 in serum and synovial fluid[J].Br J Rheumatol,1993,32(11):949-955.
[37] Vnnen T,Koskinen A,Paukkeri EL,et al. YKL-40 as a novelfactor associated with inflammation and catabolic mechanisms inosteoarthritic joints[J]. Mediators Inflamm,2014,2014:215140.
[38] Takahashi M,Naito K,Abe M,et al. Relationship between radio-graphic grading of osteoarthritis and the biochemical markers forarthritis in knee osteoarthritis[J]. Arthritis Res Ther,2004,6(3):R208-212.
[39] Takahashi KA,Tonomura H,Arai YL,et al. Hyperthermia for thetreatment of articular cartilage with osteoarthritis[J]. Int J Hyper-thermia,2009,25(8):661-667.
[40] Terauchi R,Takahashi KA,Arai Y,et al. Hsp70 prevents nitricoxide-induced apoptosis in articular chondrocytes[J]. ArthritisRheum,2003,48(6):1562-1568.
[41] Ngarmukos S,Scaramuzza S,Theerawattanapong N,et al. Circulat-ing and Synovial Fluid Heat Shock Protein 70 Are Correlated withSeverity in Knee Osteoarthritis[J]. Cartilage,2018,2018:1947603518790075.
[42] Haseeb A,Haqqi TM. Immunopathogenesis of osteoarthritis[J].Clin Immunol,2013,146(3):185-196.
[43] Wojdasiewicz P,Poniatowski LA,Szukiewicz D. The role ofinflammatory and anti-inflammatory cytokines in the pathogenesisof osteoarthritis[J]. Mediators Inflamm,2014,2014:561459.
[44] Wang T,He C. Pro-inflammatory cytokines:The link between obesityand osteoarthritis[J]. Cytokine Growth Factor Rev,2018,44:38-50.
[45] Lawrence JT,Birmingham J,Toth AP. Emerging ideas:Preventionof posttraumatic arthritis through interleukin-1 and tumor necrosisfactor-alpha inhibition[J]. Clin Orthop Relat Res,2011,469(12):3522-3526.
[46] Park SJ,Cheon EJ,Lee MH,et al. MicroRNA-127-5p regulatesmatrix metalloproteinase 13 expression and interleukin-1beta-induced catabolic effects in human chondrocytes[J]. ArthritisRheum,2013,65(12):3141-3152.
[47] Nixon AJ,Grol MW,Lang HM,et al. Disease-modifying Osteoar-thritis Treatment with Interleukin-1 Receptor Antagonist GeneTherapy in Small and Large Animal Models[J]. Arthritis Rheu-matol,2018,70:1757-1768.
[48] Conde J,Scotece M,Gomez R,et al. Adipokines and osteoarthri-tis:Novel molecules involved in the pathogenesis and progressionof disease[J]. Arthritis,2011,2011:203901.
[49] Helfer G,Wu QF. Chemerin:A multifaceted adipokine involved inmetabolic disorders[J]. J Endocrinol,2018,238(2):R79-94.
[50] Ma J,Ren L,Guo CJ,et al. Chemerin affects the metabolic andproliferative capabilities of chondrocytes by increasing the phos-phorylation of AKT/ERK[J]. Eur Rev Med Pharmacol Sci,2018,22(12):3658-3662.
[51] Berg V,Sveinbjornsson B,Bendiksen S,et al. Human articularchondrocytes express ChemR23 and chemerin; ChemR23 pro-motes inflammatory signalling upon binding the ligand chemerin(21-157)[J]. Arthritis Res Ther,2010,12(6):R228.
[52] Ma J,Niu DS,Wan NJ,et al. Elevated chemerin levels in synovial fluidand synovial membrane from patients with knee osteoarthritis[J]. Int JClin Exp Pathol,2015,8(10):13393-13398.
[2] Peat G,Duncan RC,Wood LR,et al. Clinical features of symp-tomatic patellofemoral joint osteoarthritis[J]. Arthritis Res Ther,2012,14(2):R63-63.
[3] Atherton HJ,Jones OA,Malik S,et al. A comparative metabolics-tudy of NHR-49 in Caenorhabditis elegans and PPAR-alpha inthe mouse[J]. FEBS Letters,2008,582(12):1661-1666.
[4]周晓辉,常亚南,何晓亮,等.Ⅱ型胶原蛋白的结构、功能及其最新研究进展[J].河北科技大学学报,2017,38(2):202-208.
[5] Jordan MK. Urinary CTX-Ⅱand glucosyl-galactosyl-pyridinolineare associated with the presence and severity of radiographic kneeosteoarthritis in men[J]. Ann Rheum Dis,2005,65(7):871-877.
[6] Huang MJ,Zhao JY,Huang Y,et al. Meta-analysis of urinaryC-terminal telopeptide of typeⅡcollagen as a biomarker in oste-oarthritis diagnosis[J]. J Orthop Translat,2018,13:50-57.
[7] Tanishi N,Yamagiwa H,Hayami T,et al. Relationship betweenradiological knee osteoarthritis and biochemical markers of carti-lage and bone degradation(urine CTX-Ⅱand NTX-Ⅰ):theMatsudai Knee Osteoarthritis Survey[J]. J Bone Miner Metab,2009,27(5):605-612.
[8] Park YM,Kim SJ,Lee KJ,et al. Detection of CTX-Ⅱin serumand urine to diagnose osteoarthritis by using a fluoro-microbeadsguiding chip[J]. Biosens Bioelectron,2015,67:192-199.
[9] Sharif M,Kirwan J,Charni N,et al. A 5-yr longitudinal study oftype IIA collagen synthesis and total typeⅡcollagen degradationin patients with knee osteoarthritis-association with disease pro-gression[J]. Rheumatology(Oxford),2007,46(6):938-943.
[10] KalaE,Bahlous A,Bouzid K,et al. The role of typeⅡcollagenfragments and X-ray progression of knee osteoarthritis[J]. AnnBiol Clin(Paris),2014,72(6):715-721.
[11] Huang M,Zhao J,Huang Y,et al. Meta-analysis of urinary C-ter-minal telopeptide of typeⅡcollagen as a biomarker in osteoar-thritis diagnosis[J]. J Orthop Translat,2018,13:50-57.
[12] Tanishi N,Yamagiwa H,Hayami T,et al. Usefulness of urinaryCTX-Ⅱand NTX-Ⅰin evaluating radiological knee osteoarthri-tis:the Matsudai knee osteoarthritis survey[J]. J Orthop Sci,2014,19(3):429-436.
[13] Valdes AM,Meulenbelt I,Chassaing E,et al. Large scale meta-analysis of urinary C-terminal telopeptide,serum cartilage oligo-meric protein and matrix metalloprotease degraded typeⅡcolla-gen and their role in prevalence,incidence and progression ofosteoarthritis[J]. Osteoarthritis Cartilage,2014,22:683-689.
[14] van der Kraan PM,Stoop R,Meijers TH,et al. Expression of typeⅩcollagen in young and old C57BI/6 and Balb/c mice. Relationwith articular cartilage degeneration[J]. Osteoarthritis Cartilage,2001,9(2):92-100.
[15] Girkontaite I,Frischholz S,Lammi P,et al. Immunolocalization oftypeⅩcollagen in normal fetal and adult osteoarthritic cartilagewith monoclonal antibodies[J]. Matrix Biol,1996,15(4):231-238.
[16] Zheng Q,Keller B,Zhou G,et al. Localization of the cis-enhancerelement for mouse typeⅩcollagen expression in hypertrophicchondrocytes in vivo[J]. J Bone Miner Res,2009,24(6):1022-1032.
[17] Matsumoto T,Cooper GM,Gharaibeh B,et al. Cartilage repair in arat model of osteoarthritis through intraarticular transplantation ofmuscle-derived stem cells expressing bone morphogenetic protein4 and soluble flt-1[J]. Arthritis Rheum, 2009,60(5):1390-1405.
[18] Gu J,Lu Y,Li F,et al. Identification and characterization of thenovel Col10a1 regulatory mechanism during chondrocyte hyper-trophic differentiation[J]. Cell Death Dis,2014,5(10):e1469.
[19] He Y,Siebuhr AS,Brandt-Hansen NU,et al. TypeⅩcollagenlevels are elevated in serum from human osteoarthritis patientsand associated with biomarkers of cartilage degradation andinflammation[J]. BMC Musculoskelet Disord,2014,15(1):309.
[20] Gheita TA,El-Awar AH,El-Ansary MM,et al. Cartilage oligomericmatrix protein(COMP)levels in serum and synovial fluid inosteoarthritis(OA)patients:Correlation with clinical,radiologi-cal and laboratory parameters[J]. Osteoarthritis Cartilage,2015,23(2):A85-A85.
[21] Salminen H,Perala M,Lorenzo P,et al. Up-regulation of cartilageoligomeric matrix protein at the onset of articular cartilage degene-ration in a transgenic mouse model of osteoarthritis[J]. ArthritisRheum,2000,43(8):1742-1748.
[22] Sharif M,Kirwan JR,Elson CJ,et al. Suggestion of nonlinear orphasic progression of knee osteoarthritis based on measurements ofserum cartilage oligomeric matrix protein levels over five years[J].Arthritis Rheum,2004,50(8):2479-2488.
[23] Attur M,Krasnokutskysamuels S,Samuels J,et al. Prognosticbiomarkers in osteoarthritis[J]. Curr Opin Rheumatol,2013,25(1):136-144.
[24] Kaspiris A,Khaldi L,Chronopoulos E,et al. Macrophage-specificmetalloelastase(MMP-12)immunoexpression in the osteochondralunit in osteoarthritis correlates with BMI and disease severity[J].Pathophysiology,2015,22:143-151.
[25] HulejováH,BaresováV,Klézl Z,et al. Increased level of cyto-kines and matrix metalloproteinases in osteoarthritic subchondralbone[J]. Cytokine,2007,38(3):151-156.
[26] Pengas I,Eldridge S,Assiotis A,et al. MMP-3 in the peripheralserum as a biomarker of knee osteoarthritis,40 years after opentotal knee meniscectomy[J]. J Exp Orthop,2018,5(1):21.
[27] Wang W,Lian N,Li L,et al. Atf4 regulates chondrocyte prolifera-tion and differentiation during endochondral ossification by activa-ting Ihh transcription[J]. Development,2009,136(24):4143-4153.
[28] Wei F,Zhou J,Wei X,et al. Activation of Indian hedgehog pro-motes chondrocyte hypertrophy and upregulation of MMP-13 inhuman osteoarthritic cartilage[J]. Osteoarthritis Cartilage,2012,20(7):755-763.
[29] Zhou J,Wei X,Wei L. Indian Hedgehog,a critical modulator inosteoarthritis,could be a potential therapeutic target for attenua-ting cartilage degeneration disease[J]. Connect Tissue Res,2014,55(4):257-261.
[30] Zhang C,Wei X,Chen C,et al. Indian hedgehog in synovial fluid is anovel marker for early cartilage lesions in human knee joint[J]. Int JMol Sci,2014,15(5):7250-7265.
[31] Ozaki E,Campbell M,Doyle SL. Targeting the NLRP3 inflamma-some in chronic inflammatory diseases:Current perspectives[J].J Inflamm Res,2015,8:15-27.
[32] Mc Allister MJ,Chemaly M,Eakin AJ,et al. NLRP3 as a poten-tially novel biomarker for the management of osteoarthritis[J].Osteoarthritis Cartilage,2018,26(5):612-619.
[33] Clavijo-Cornejo D,Martínez-Flores K,Silva-Luna K,et al. TheOverexpression of NALP3 Inflammasome in Knee Osteoarthritis IsAssociated with Synovial Membrane Prolidase and NADPH Oxi-dase 2[J]. Oxid Med Cell Longev,2016,2016:1472567.
[34] Jin C,Frayssinet P,Pelker R,et al. NLRP3 inflammasome plays acritical role in the pathogenesis of hydroxyapatite-associatedarthropathy[J]. Proc Natl Acad Sci U S A,2011,108(36):14867-14872.
[35] Scanzello CR,Goldring SR. The role of synovitis in osteoarthritispathogenesis[J]. Bone,2012,51(2):249-257.
[36] Johansen JS,Jensen HS,Price PA. A new biochemical marker forjoint injury. Analysis of YKL-40 in serum and synovial fluid[J].Br J Rheumatol,1993,32(11):949-955.
[37] Vnnen T,Koskinen A,Paukkeri EL,et al. YKL-40 as a novelfactor associated with inflammation and catabolic mechanisms inosteoarthritic joints[J]. Mediators Inflamm,2014,2014:215140.
[38] Takahashi M,Naito K,Abe M,et al. Relationship between radio-graphic grading of osteoarthritis and the biochemical markers forarthritis in knee osteoarthritis[J]. Arthritis Res Ther,2004,6(3):R208-212.
[39] Takahashi KA,Tonomura H,Arai YL,et al. Hyperthermia for thetreatment of articular cartilage with osteoarthritis[J]. Int J Hyper-thermia,2009,25(8):661-667.
[40] Terauchi R,Takahashi KA,Arai Y,et al. Hsp70 prevents nitricoxide-induced apoptosis in articular chondrocytes[J]. ArthritisRheum,2003,48(6):1562-1568.
[41] Ngarmukos S,Scaramuzza S,Theerawattanapong N,et al. Circulat-ing and Synovial Fluid Heat Shock Protein 70 Are Correlated withSeverity in Knee Osteoarthritis[J]. Cartilage,2018,2018:1947603518790075.
[42] Haseeb A,Haqqi TM. Immunopathogenesis of osteoarthritis[J].Clin Immunol,2013,146(3):185-196.
[43] Wojdasiewicz P,Poniatowski LA,Szukiewicz D. The role ofinflammatory and anti-inflammatory cytokines in the pathogenesisof osteoarthritis[J]. Mediators Inflamm,2014,2014:561459.
[44] Wang T,He C. Pro-inflammatory cytokines:The link between obesityand osteoarthritis[J]. Cytokine Growth Factor Rev,2018,44:38-50.
[45] Lawrence JT,Birmingham J,Toth AP. Emerging ideas:Preventionof posttraumatic arthritis through interleukin-1 and tumor necrosisfactor-alpha inhibition[J]. Clin Orthop Relat Res,2011,469(12):3522-3526.
[46] Park SJ,Cheon EJ,Lee MH,et al. MicroRNA-127-5p regulatesmatrix metalloproteinase 13 expression and interleukin-1beta-induced catabolic effects in human chondrocytes[J]. ArthritisRheum,2013,65(12):3141-3152.
[47] Nixon AJ,Grol MW,Lang HM,et al. Disease-modifying Osteoar-thritis Treatment with Interleukin-1 Receptor Antagonist GeneTherapy in Small and Large Animal Models[J]. Arthritis Rheu-matol,2018,70:1757-1768.
[48] Conde J,Scotece M,Gomez R,et al. Adipokines and osteoarthri-tis:Novel molecules involved in the pathogenesis and progressionof disease[J]. Arthritis,2011,2011:203901.
[49] Helfer G,Wu QF. Chemerin:A multifaceted adipokine involved inmetabolic disorders[J]. J Endocrinol,2018,238(2):R79-94.
[50] Ma J,Ren L,Guo CJ,et al. Chemerin affects the metabolic andproliferative capabilities of chondrocytes by increasing the phos-phorylation of AKT/ERK[J]. Eur Rev Med Pharmacol Sci,2018,22(12):3658-3662.
[51] Berg V,Sveinbjornsson B,Bendiksen S,et al. Human articularchondrocytes express ChemR23 and chemerin; ChemR23 pro-motes inflammatory signalling upon binding the ligand chemerin(21-157)[J]. Arthritis Res Ther,2010,12(6):R228.
[52] Ma J,Niu DS,Wan NJ,et al. Elevated chemerin levels in synovial fluidand synovial membrane from patients with knee osteoarthritis[J]. Int JClin Exp Pathol,2015,8(10):13393-13398.