| [1] Goldring MB, Goldring SR.Osteoarthritis. J Cell Physiol. 2007; 213(3):626-634.[2] Davis AM, MacKay C.Osteoarthritis year in review: outcome of rehabilitation. Osteoarthritis Cartilage.2013;21(10):1414- 1424.[3] Cushnaghan J, Dieppe P.Study of 500 patients with limb joint osteoarthritis. I. Analysis by age, sex, and distribution of symptomatic joint sites. Ann Rheum Dis. 1991;50(1):8-13.[4] Johnson VL, Hunter DJ.The epidemiology of osteoarthritis. Best Pract Res Clin Rheumatol. 2014; 28(1):5-15.[5] Zhang J, Song L, Liu G, et al.Risk factors for and prevalence of knee osteoarthritis in the rural areas of Shanxi Province, North China: a COPCORD study. Rheumatology international. 2013;33(11):2783-2788.[6] Jiang L, Rong J, Zhang Q, et al.Prevalence and associated factors of knee osteoarthritis in a community-based population in Heilongjiang, Northeast China. Rheumatology international.2012;32(5):1189-1195.[7] Li Y, Wei X, Zhou J, et al.The age-related changes in cartilage and osteoarthritis. BioMed research international. 2013;2013: 916530.[8] Felson DT, Naimark A, Anderson J, et al.The prevalence of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis and rheumatism. 1987;30(8): 914-918.[9] Allam H, Mohammed NH.The Role of Scalp Acupuncture for Relieving the Chronic Pain of Degenerative Osteoarthritis: A Pilot Study of Egyptian Women. Medical acupuncture. 2013; 25(3):216-220.[10] Dieppe PA, Lohmander LS.Pathogenesis and management of pain in osteoarthritis. Lancet.2005;365(9463):965-973.[11] Funck-Brentano T, Cohen-Solal M.Subchondral bone and osteoarthritis. Current opinion in rheumatology.2015;27(4): 420-426.[12] Chen YF, Jobanputra P, Barton P, et al.Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation. Health technology assessment.2008;12(11):1-278, iii.[13] Felson DT, Zhang Y.An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis and rheumatism.1998;41(8):1343-1355.[14] Huskisson EC.Pharmacologic and non-drug therapies for osteoarthritis. Scand J Rheumatol Suppl 1988;77:34-36.[15] Simon LS.OARSI Clinical Trials Recommendations: An abbreviated regulatory guide to the clinical requirements for development of therapeutics in osteoarthritis. Osteoarthritis Cartilage 2015;23(5):674-676.[16] Clouet J, Vinatier C, Merceron C, et al.From osteoarthritis treatments to future regenerative therapies for cartilage. Drug Discov Today.2009; 14(19-20):913-925.[17] Lapane KL, Yang S, Driban JB, et al.Effects of prescription nonsteroidal antiinflammatory drugs on symptoms and disease progression among patients with knee osteoarthritis. Arthritis Rheumatol.2015;67(3):724-732.[18] Chandanwale AS, Sundar S, Latchoumibady K, et al. Efficacy and safety profile of combination of tramadol-diclofenac versus tramadolparacetamol in patients with acute musculoskeletal conditions, postoperative pain, and acute flare of osteoarthritis and rheumatoid arthritis: a phase III, 5-day open-label study. J Pain Res.2014;7:455-463.[19] Essex MN, Behar R, O'Connell MA, et al. Efficacy and tolerability of celecoxib and naproxen versus placebo in Hispanic patients with knee osteoarthritis. Int J Gen Med. 2014;7:227-235.[20] Hochberg MC, Martel-Pelletier J, Monfort J, et al. Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib.Ann Rheum Dis. 2016;75(1):37-44.[21] Kingsbury SR, Tharmanathan P,Arden NK, et al. Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial of treatment effectiveness (PROMOTE): study protocol for a randomized controlled trial. Trials.2015;16:77.[22] Chevalier X, Ravaud P, Maheu E, et al. Adalimumab in patients with hand osteoarthritis refractory to analgesics and NSAIDs: a randomised, multicentre, double-blind, placebo-controlled trial. Ann Rheum Dis.2015;74:1697-705.[23] Bruyere O, Reginster JY, Bellamy N,et al.Clinically meaningful effect of strontium ranelate on symptoms in knee osteoarthritis: a responder analysis. Rheumatol (Oxford). 2014;53(8):1457-1464.[24] Laslett LL, Kingsbury SR, Hensor EM,et al.Effect of bisphosphonate use in patients with symptomatic and radiographic knee osteoarthritis: data from the Osteoarthritis Initiative. Ann Rheum Dis.2014;73(5):824-830.[25] Schnitzer TJ, Ekman EF, Spierings EL, et al. Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain.Ann Rheum Dis 2015;74(6):1202-1211.[26] Balanescu AR, Feist E, Wolfram G, et al. Efficacy and safety of tanezumab added on to diclofenac sustained release in patients with knee or hip osteoarthritis: a double-blind, placebo-controlled, parallelgroup, multicentre phase III randomised clinical trial. Ann Rheum Dis.2014;73(9):1665-1672.[27] Tiseo PJ, Kivitz AJ, Ervin JE, et al. Fasinumab (REGN475), an antibody against nerve growth factor for the treatment of pain: results from a double-blind, placebocontrolled exploratory study in osteoarthritis of the knee.Pain. 2014; 155(7):1245-1252.[28] Kodama N, Takemura Y, Ueba H, et al.A new form of surgical treatment for patients with avascular necrosis of the talus and secondary osteoarthritis of the ankle. Bone Joint J.2015; 97-B(6):802-808.[29] Nejati P, Farzinmehr A, Moradi-Lakeh M.The effect of exercise therapy on knee osteoarthritis: a randomized clinical trial. Med J Islam Repub Iran..2015;29:186.[30] Yeh HJ, Chou YJ, Yang NP, et al.Receipt of physical therapy among osteoarthritis patients and its influencing factors. Archives of physical medicine and rehabilitation.2015;96(6): 1021-1027.[31] Rosemann T, Laux G, Szecsenyi J, et al.Pain and osteoarthritis in primary care: factors associated with pain perception in a sample of 1,021 patients. Pain medicine.2008;9(7):903-910.[32] Sulzbacher I. Osteoarthritis: histology and pathogenesis. Wiener medizinische Wochenschrift.2013;163(9-10):212-219.[33] Goldring MB, Tsuchimochi K, Ijiri K.The control of chondrogenesis. J Cell Biochem.2006; 97 (1): 33-44.[34] Shane Anderson A, Loeser RF. Why is osteoarthritis an age-related disease? Best Pract Res Clin Rheumatol. 2010; 24(1):15-26.[35] Findlay DM, Atkins GJ.Osteoblast-chondrocyte interactions in osteoarthritis. Current osteoporosis reports. 2014;12(1): 127-134.[36] Malemud CJ.Biologic basis of osteoarthritis: state of the evidence. Current opinion in rheumatology.2015;27(3):289-294.[37] Loeser RF.Age-related changes in the musculoskeletal system and the development of osteoarthritis.Clinics in geriatric medicine.2010;26(3):371-386.[38] van der Kraan PM, van den Berg WB: Osteoarthritis in the context of ageing and evolution. Loss of chondrocyte differentiation block during ageing. Ageing Research Reviews. 2008;7(2):106-113.[39] Wang X, Zhao X, Tang S.Inhibitory effects of EGb761 on the expression of matrix metalloproteinases (MMPs) and cartilage matrix destruction. Cell Stress Chaperones. 2015;20(5): 781-786.[40] Tiku ML, Sabaawy HE.Cartilage regeneration for treatment of osteoarthritis: a paradigm for nonsurgical intervention. Therapeutic advances in musculoskeletal disease.2015;7(3): 76-87.[41] Wluka AE, Ding C, Wang Y, et al.Aspirin is associated with reduced cartilage loss in knee osteoarthritis: Data from a cohort study. Maturitas. 2015;22(3):S243-S244.[42] Mickiewicz B, Kelly JJ, Ludwig TE, et al.Metabolic analysis of knee synovial fluid as a potential diagnostic approach for osteoarthritis. J Orthop Res. 2015;33(11):1631-1638. [43] Zeng C, Li YS, Lei GH.Synovitis in knee osteoarthritis: a precursor or a concomitant feature? Ann Rheum Dis. 2015; 74(10):e58.[44] Henrotin Y, Lambert C, Richette P.Importance of synovitis in osteoarthritis: evidence for the use of glycosaminoglycans against synovial inflammation. Semin Arthritis Rheum. 2014; 43(5):579-587.[45] Sharkey PF, Cohen SB, Leinberry CF, et al.Subchondral bone marrow lesions associated with knee osteoarthritis. Am J Orthop (Belle Mead NJ). 2012;41(9):413-417.[46] Bousson V, Lowitz T, Laouisset L, et al.CT imaging for the investigation of subchondral bone in knee osteoarthritis. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2012;23 Suppl 8:S861-865.[47] Blander G, Guarente L.The Sir2 family of protein deacetylases. Annu Rev Biochem. 2004;73:417-435.[48] Frye RA.Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochemical and biophysical research communications.2000; 273(2):793-798.[49] Dali-Youcef N, Lagouge M, Froelich S, et al.Sirtuins: the 'magnificent seven', function, metabolism and longevity. Annals of medicine.2007;39(5):335-345.[50] Kwon HS, Ott M.The ups and downs of SIRT1. Trends in biochemical sciences.2008; 33(11):517-525.[51] Ryall JG, Dell'Orso S, Derfoul A, et al.The NAD(+)-dependent SIRT1 deacetylase translates a metabolic switch into regulatory epigenetics in skeletal muscle stem cells. Cell stem cell.2015;16(2):171-183.[52] Kim MY, Lim JH, Youn HH, et al.Resveratrol prevents renal lipotoxicity and inhibits mesangial cell glucotoxicity in a manner dependent on the AMPK-SIRT1-PGC1alpha axis in db/db mice. Diabetologia.2013;56(1):204-217.[53] Michan S, Sinclair D.Sirtuins in mammals: insights into their biological function. Biochem J. 2007;404(1):1-13.[54] Seo JS, Moon MH, Jeong JK, et al.SIRT1, a histone deacetylase, regulates prion protein-induced neuronal cell death. Neurobiol Aging. 2012;33(6):1110-1120.[55] Liu T, Liu PY, Marshall GM.The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res.2009; 69(5):1702-1705.[56] Choi HN, Bae JS, Jamiyandorj U, et al.Expression and role of SIRT1 in hepatocellular carcinoma. Oncology Reports. 2011; 26(2):503-510.[57] Biswas AK, Johnson DG.Transcriptional and nontranscriptional functions of E2F1 in response to DNA damage. Cancer Res.2012;72(1):13-17.[58] Revollo JR, Li X.The ways and means that fine tune Sirt1 activity. Trends in biochemical sciences.2013;38(3):160-167.[59] Olmos Y, Brosens JJ, Lam EW.Interplay between SIRT proteins and tumour suppressor transcription factors in chemotherapeutic resistance of cancer. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.2011;14(1):35-44.[60] Yamakuchi M. MicroRNA Regulation of SIRT1. Frontiers in physiology.2012;3:68.[61] Guo X, Williams JG, Schug TT, et al.DYRK1A and DYRK3 promote cell survival through phosphorylation and activation of SIRT1.J Biol Chem. 2010;285(17):13223-13232.[62] Liu X, Wang D, Zhao Y, et al.Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1). Proceedings of the National Academy of Sciences of the United States of America.2011;108(5):1925-1930.[63] Kornberg MD, Sen N, Hara MR, et al.GAPDH mediates nitrosylation of nuclear proteins. Nature Cell Biology. 2010; 12(11):1094-1100.[64] Lin Z, Yang H, Kong Q, et al.USP22 antagonizes p53 transcriptional activation by deubiquitinating Sirt1 to suppress cell apoptosis and is required for mouse embryonic development. Molecular cell.2012;46(4):484-494.[65] Fusco S, Maulucci G, Pani G.Sirt1: def-eating senescence? Cell cycle.2012; 11(22):4135-4146.[66] Takayama K, Ishida K, Matsushita T, et al.SIRT1 regulation of apoptosis of human chondrocytes. Arthritis and rheumatism. 2009;60(9):2731-2740.[67] Hong EH, Lee SJ, Kim JS, et al.Ionizing radiation induces cellular senescence of articular chondrocytes via negative regulation of SIRT1 by p38 kinase. J Biol Chem. 2010;285(2): 1283-1295.[68] Gagarina V, Gabay O, Dvir-Ginzberg M, et al.SirT1 enhances survival of human osteoarthritic chondrocytes by repressing protein tyrosine phosphatase 1B and activating the insulin-like growth factor receptor pathway.Arthritis and rheumatism. 2010;62(5):1383-1392.[69] Kim HJ, Braun HJ, Dragoo JL.The effect of resveratrol on normal and osteoarthritic chondrocyte metabolism. Bone Joint Res. 2014 ;3(3):51-59.[70] Dvir-Ginzberg M, Gagarina V, Lee EJ, et al.Tumor necrosis factor alpha-mediated cleavage and inactivation of SirT1 in human osteoarthritic chondrocytes. Arthritis Rheumatism. 2011;63(8):2363-2373.[71] Moon MH, Jeong JK, Lee YJ, et al.SIRT1, a class III histone deacetylase, regulates TNF-alpha-induced inflammation in human chondrocytes. Osteoarthritis Cartilage. 2013;21(3): 470-480.[72] Dvir-Ginzberg M, Gagarina V, Lee EJ, et al.Regulation of cartilage-specific gene expression in human chondrocytes by SirT1 and nicotinamide phosphoribosyltransferase. J Biol Chem. 2008;283(52):36300-36310.[73] Fujita N, Matsushita T, Ishida K, et al.Potential involvement of SIRT1 in the pathogenesis of osteoarthritis through the modulation of chondrocyte gene expressions. J Orthop Res. 2011;29(4):511-515.[74] Matsushita T, Sasaki H, Takayama K, et al.The overexpression of SIRT1 inhibited osteoarthritic gene expression changes induced by interleukin-1beta in human chondrocytes. J Orthop Res.2013;31(4):531-537.[75] Gabay O, Sanchez C, Dvir-Ginzberg M, et al.Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model.Arthritis Rheum. 2013;65(1):159-166.[76] Li W, Cai L, Zhang Y, et al.Intra-articular resveratrol injection prevents osteoarthritis progression in a mouse model by activating SIRT1 and thereby silencing HIF-2alpha. J Orthop Res.2015;33(7):1061-1070.[77] Lim HD, Kim YS, Ko SH, et al.Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway. J Pineal Res. 2012;53(3):225-237.[78] McBurney MW, Yang X, Jardine K, et al.The mammalian SIR2alpha protein has a role in embryogenesis and gametogenesis. Mol Cell Biol. 2003;23(1):38-54. [79] Matsuzaki T, Matsushita T, Takayama K, et al.Disruption of Sirt1 in chondrocytes causes accelerated progression of osteoarthritis under mechanical stress and during ageing in mice. Ann Rheum Dis. 2014;73(7):1397-1404.[80] Xu F, Gao Z, Zhang J, et al.Lack of SIRT1 (Mammalian Sirtuin 1) activity leads to liver steatosis in the SIRT1+/- mice: a role of lipid mobilization and inflammation. Endocrinology. 2010;1 51(6):2504-2514.[81] Gabay O, Oppenhiemer H, Meir H, et al.Increased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice.Ann Rheum Dis. 2012;71(4):613-616.[82] Seifert EL, Caron AZ, Morin K, et al.SirT1 catalytic activity is required for male fertility and metabolic homeostasis in mice. FASEB J. 2012;26(2):555-566.[83] Gabay O, Zaal KJ, Sanchez C, et al.Sirt1-deficient mice exhibit an altered cartilage phenotype. Joint Bone Spine. 2013;80(6):613-620. |
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文题释义：
沉默信息调节因子1：是目前研究最为广泛的sirtuin蛋白，也是近年来热门的一个药物设计靶标。沉默信息调节因子1广泛参与脂肪酸氧化、应激耐受、胰岛素分泌和葡萄糖合成等生理活动，这些生理活动与2型糖尿病、心血管疾病、代谢综合征、炎症和衰老等密切相关。已有研究发现，促进沉默信息调节因子1酶活能够延长低等生物的寿命，对2型糖尿病肥胖小鼠也有较好的治疗作用。
骨关节炎：为一种退行性病变，系由于增龄、肥胖、劳损、创伤、关节先天性异常、关节畸形等诸多因素引起的关节软骨退化损伤、关节边缘和软骨下骨反应性增生，又称骨关节病、退行性关节炎、老年性关节炎、肥大性关节炎等。临床表现为缓慢发展的关节疼痛、压痛、僵硬、关节肿胀、活动受限和关节畸形等。
.jpg)
文题释义：
沉默信息调节因子1：是目前研究最为广泛的sirtuin蛋白，也是近年来热门的一个药物设计靶标。沉默信息调节因子1广泛参与脂肪酸氧化、应激耐受、胰岛素分泌和葡萄糖合成等生理活动，这些生理活动与2型糖尿病、心血管疾病、代谢综合征、炎症和衰老等密切相关。已有研究发现，促进沉默信息调节因子1酶活能够延长低等生物的寿命，对2型糖尿病肥胖小鼠也有较好的治疗作用。
骨关节炎：为一种退行性病变，系由于增龄、肥胖、劳损、创伤、关节先天性异常、关节畸形等诸多因素引起的关节软骨退化损伤、关节边缘和软骨下骨反应性增生，又称骨关节病、退行性关节炎、老年性关节炎、肥大性关节炎等。临床表现为缓慢发展的关节疼痛、压痛、僵硬、关节肿胀、活动受限和关节畸形等。