Is osteoarthritis a metabolic disorder?

British Medical Bulletin

Volumn 115, Issue 1, 2015, Pages 111-121

  Kluzek, S ^a   Newton, J L ^a,c   Arden, N K ^a,b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^c UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

adipokines; metabolic syndrome; osteoarthritis

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; LEPTIN; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; RESISTIN;

ADIPOSE TISSUE; ARTHRALGIA; ARTICLE; CARDIOVASCULAR DISEASE; COHORT ANALYSIS; DYSLIPIDEMIA; HAND OSTEOARTHRITIS; HIP OSTEOARTHRITIS; HUMAN; IN VIVO STUDY; INFLAMMATION; KNEE OSTEOARTHRITIS; METABOLIC DISORDER; METABOLIC SYNDROME X; MORTALITY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; OSTEOARTHRITIS; PRIORITY JOURNAL; RISK ASSESSMENT; RISK FACTOR; ANIMAL; COMPLICATION; PHYSIOLOGY;

ADIPOKINES; ANIMALS; HUMANS; INFLAMMATION; METABOLIC SYNDROME X; OBESITY; OSTEOARTHRITIS; RISK FACTORS;

EID: 84941199951     PISSN: 00071420     EISSN: 14718391     Source Type: Journal    
DOI: 10.1093/bmb/ldv028     Document Type: Article

References (124)

1. Romeo GR, Lee J, Shoelson SE. Metabolic syndrome, insulin resistance, and roles of inflammation-mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol 2012;32:1771-6.
2. Jung UJ, Choi MS. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dysli-pidemia and nonalcoholic fatty liver disease. Int J Mol Sci 2014;15:6184-223.
3. Felson DT, Anderson JJ, Naimark A, et al. Obesity and knee osteoarthritis. The Framingham Study. Ann Intern Med 1988;109:18-24.
4. Hart DJ, Spector TD. The relationship of obesity, fat distribution and osteoarthritis in women in the general population: the Chingford Study. J Rheumatol 1993;20: 331-5.
5. Puenpatom RA, Victor TW. Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data. Postgrad Med 2009; 121:9-20.
6. Engstrom G, Gerhardsson de Verdier M, Rollof J, et al. C-reactive protein, metabolic syndrome and incidence of severe hip and knee osteoarthritis. A population-based cohort study. Osteoarthritis Cartilage 2009;17: 168-73.
7. Sturmer T, Sun Y, Sauerland S, et al. Serum cholesterol and osteoarthritis. The baseline examination of the Ulm Osteoarthritis Study. J Rheumatol 1998;25:1827-32.
8. Yoshimura N, Muraki S, Oka H, et al. Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study. Osteoarthritis Cartilage 2012;20:1217-26.
9. Marshall M, Peat G, Nicholls E, et al. Subsets of symptomatic hand osteoarthritis in community-dwelling older adults in the United Kingdom: prevalence, interrelationships, risk factor profiles and clinical characteristics at baseline and 3-years. Osteoarthritis Cartilage 2013;21: 1674-84.
10. Sturmer T, Brenner H, Brenner RE, et al. Non-insulin dependent diabetes mellitus (NIDDM) and patterns of osteoarthritis. The Ulm osteoarthritis study. Scand J Rheumatol 2001;30:169-71.
11. Schett G, Kleyer A, Perricone C, et al. Diabetes is an independent predictor for severe osteoarthritis: results from a longitudinal cohort study. Diabetes Care 2013;36:403-9.
12. Hawker GA, Croxford R, Bierman AS, et al. All-cause mortality and serious cardiovascular events in people with hip and knee osteoarthritis: a population based cohort study. PLoS ONE 2014;9:e91286.
13. Nuesch E, Dieppe P, Reichenbach S, et al. All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ 2011;342:d1165.
14. Haugen IK, Ramachandran VS, Misra D, et al. Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham Heart Study. Ann Rheum Dis 2015;74:74-81.
15. Murphy L, Schwartz TA, Helmick CG, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum 2008;59:1207-13.
16. Culliford DJ, Maskell J, Kiran A, et al. The lifetime risk of total hip and knee arthroplasty: results from the UK general practice research database. Osteoarthritis Cartilage 2012;20:519-24.
17. Loeser RF, Goldring SR, Scanzello CR, et al. Osteoarth-ritis: a disease of the joint as an organ. Arthritis Rheum 2012;64:1697-707.
18. Han TS, Lee DM, Lean M, et al. Associations of obesity with socioeconomic and lifestyle factors in middle-aged and elderly men: European Male Aging Study (EMAS). Eur J Endocrinol 2015;172:59-67.
19. Lohmander LS, Gerhardsson de Verdier M, Rollof J, et al. Incidence of severe knee and hip osteoarthritis in relation to different measures of body mass: a population-based prospective cohort study. Ann Rheum Dis 2009;68:490-6.
20. Lindsay RS, Howard BV. Cardiovascular risk associated with the metabolic syndrome. Curr Diab Rep 2004;4: 63-8.
21. Hart DJ, Doyle DV, Spector TD. Association between metabolic factors and knee osteoarthritis in women: the Chingford Study. J Rheumatol 1995;22:1118-23.
22. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112: 2735-52.
23. Wilson PW, D'Agostino RB, Parise H, et al. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 2005;112: 3066-72.
24. Liu Q, Niu J, Huang J, et al. Knee osteoarthritis and all-cause mortality: The Wuchuan Osteoarthritis Study. Osteoarthritis Cartilage 2015;23:1154-7.
25. Graves BW. The obesity epidemic: scope of the problem and management strategies. J Midwifery Womens Health 2010;55:568-78.
26. Blagojevic M, Jinks C, Jeffery A, et al. Risk factors for onset of osteoarthritis of the knee in older adults: a systematic review and meta-analysis. Osteoarthritis Cartilage 2010;18:24-33.
27. Lee R, Kean WF. Obesity and knee osteoarthritis. Inflammopharmacology 2012;20:53-8.
28. Grotle M, Hagen KB, Natvig B, et al. Obesity and osteo-arthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord 2008;9:132.
29. Yusuf E, Nelissen RG, Ioan-Facsinay A, et al. Association between weight or body mass index and hand osteoarthritis: a systematic review. Ann Rheum Dis 2010;69:761-5.
30. Cooper C, Inskip H, Croft P, et al. Individual risk factors for hip osteoarthritis: obesity, hip injury, and physical activity. Am J Epidemiol 1998;147:516-22.
31. Dahaghin S, Bierma-Zeinstra SMA, Reijman M, et al. Does hand osteoarthritis predict future hip or knee osteoarthritis? Arthritis Rheum 2005;52:3520-7.
32. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002;287:356-9.
33. Magi L, Stramenga C, Morosini P. Prevalence of the metabolic syndrome among Italian adults. Findings from the SIMAP study. Recenti Prog Med 2005;96: 280-3.
34. Singh G, Miller JD, Lee FH, et al. Prevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: data from the Third National Health and Nutrition Examination Survey. Am J Manag Care 2002;8:S383-91.
35. Han CD, Yang IH, Lee WS, et al. Correlation between metabolic syndrome and knee osteoarthritis: data from the Korean National Health and Nutrition Examination Survey (KNHANES). BMC Public Health 2013; 13:603.
36. Visser AW, de Mutsert R, le Cessie S, et al. The relative contribution of mechanical stress and systemic processes in different types of osteoarthritis: the NEO study. Ann Rheum Dis 2014 [Epub ahead of print].
37. Monira Hussain S, Wang Y, Cicuttini FM, et al. Incidence of total knee and hip replacement for osteoarth-ritis in relation to the metabolic syndrome and its components: a prospective cohort study. Semin Arthritis Rheum 2014;43:429-36.
38. Shin D. Association between metabolic syndrome, radiographic knee osteoarthritis, and intensity of knee pain: results of a national survey. J Clin Endocrinol Metab 2014;99:3177-83.
39. Yoshimura N, Muraki S, Oka H, et al. Association of knee osteoarthritis with the accumulation of metabolic risk factors such as overweight, hypertension, dyslipide-mia, and impaired glucose tolerance in Japanese men and women: the ROAD study. J Rheumatol 2011;38:921-30.
40. Gandhi R, Razak F, Davey JR, et al. Metabolic syndrome and the functional outcomes of hip and knee arthroplasty. J Rheumatol 2010;37:1917-22.
41. Gandhi R, Santone D, Takahashi M, et al. Inflammatory predictors of ongoing pain 2 years following knee replacement surgery. Knee 2013;20:316-8.
42. Koh KK, Han SH, Quon MJ. Inflammatory markers and the metabolic syndrome: insights from therapeutic interventions. J Am Coll Cardiol 2005;46:1978-85.
43. Hotamisligil GS. Inflammation and metabolic disorders. Nature 2006;444:860-7.
44. Proenca AR, Sertie RA, Oliveira AC, et al. New concepts in white adipose tissue physiology. Braz J Med Biol Res 2014;47:192-205.
45. Molica F, Morel S, Kwak BR, et al. Adipokines at the crossroad between obesity and cardiovascular disease. Thromb Haemost 2015;113:553-66.
46. de Faria AP, Modolo R, Fontana V, et al. Adipokines: novel players in resistant hypertension. J Clin Hypertens (Greenwich) 2014;16:754-9.
47. Allison MA, Jenny NS, McClelland RL, et al. The associations of adipokines with selected markers of the renin-angiotensinogen-aldosterone system: the multiethnic study of atherosclerosis. J Hum Hypertens 2014; 29:127-33.
48. Ebert T, Roth I, Richter J, et al. Different associations of adipokines in lean and healthy adults. Horm Metab Res 2014;46:41-7.
49. Meyvis K, Verrijken A, Wouters K, et al. Plasma adipo-nectin level is inversely correlated with albuminuria in overweight and obese nondiabetic individuals. Metabolism 2013;62:1570-6.
50. Ntaios G, Gatselis NK, Makaritsis K, et al. Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis 2013;227:216-21.
51. Ukkola O, Santaniemi M. Adiponectin: a link between excess adiposity and associated comorbidities? J Mol Med (Berl) 2002;80:696-702.
52. Levesque J, Lamarche B. The metabolic syndrome: definitions, prevalence and management. J Nutrigenet Nutrigenomics 2008;1:100-8.
53. Ruige JB, Dekker JM, Blum WF, et al. Leptin and variables of body adiposity, energy balance, and insulin resistance in a population-based study. The Hoorn Study. Diabetes Care 1999;22:1097-104.
54. Zimmet P, Hodge A, Nicolson M, et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoans: cross sectional study. BMJ 1996;313:965-9.
55. Moller DE, Kaufman KD. Metabolic syndrome: a clinical and molecular perspective. Annu Rev Med 2005; 56:45-62.
56. Franks PW, Brage S, Luan J, et al. Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity. Obes Res 2005;13:1476-84.
57. Ahima RS, Qi Y, Singhal NS. Adipokines that link obesity and diabetes to the hypothalamus. Prog Brain Res 2006;153:155-74.
58. Li WC, Hsiao KY, Chen IC, et al. Serum leptin is associated with cardiometabolic risk and predicts metabolic syndrome in Taiwanese adults. Cardiovasc Diabetol 2011;10:36.
59. Chiu FH, Chuang CH, Li WC, et al. The association of leptin and C-reactive protein with the cardiovascular risk factors and metabolic syndrome score in Taiwanese adults. Cardiovasc Diabetol 2012;11:40.
60. Goldring MB, Otero M. Inflammation in osteoarthritis. Curr Opin Rheumatol 2011;23:471-8.
61. Jin X, Beguerie JR, Zhang W, et al. Circulating C reactive protein in osteoarthritis: a systematic review and meta-analysis. Ann Rheum Dis 2015;74:703-10.
62. Stannus OP, Jones G, Blizzard L, et al. Associations between serum levels of inflammatory markers and change in knee pain over 5 years in older adults: a prospective cohort study. Ann Rheum Dis 2013;72: 535-40.
63. Stannus O, Jones G, Cicuttini F, et al. Circulating levels of IL-6 and TNF-alpha are associated with knee radio-graphic osteoarthritis and knee cartilage loss in older adults. Osteoarthritis Cartilage 2010;18:1441-7.
64. Livshits G, Zhai G, Hart DJ, et al. Interleukin-6 is a significant predictor of radiographic knee osteoarthritis: the Chingford Study. Arthritis Rheum 2009;60:2037-45.
65. Blumenfeld O, Williams FM, Valdes A, et al. Association of interleukin-6 gene polymorphisms with hand osteoarthritis and hand osteoporosis. Cytokine 2014;69:94-101.
66. Valdes AM, Arden NK, Tamm A, et al. A meta-analysis of interleukin-6 promoter polymorphisms on risk of hip and knee osteoarthritis. Osteoarthritis Cartilage 2010; 18:699-704.
67. Ai Z, Ning X, Shou T, et al. Association of interleukin-6 promoter polymorphism with knee osteoarthritis: a meta-analysis. Chin Med J (Engl) 2014;127:2492-6.
68. Vlad SC, Neogi T, Aliabadi P, et al. No association between markers of inflammation and osteoarthritis of the hands and knees. J Rheumatol 2011;38:1665-70.
69. Livshits G, Zhai G, Hart DJ, et al. Association between cartilage and bone biomarkers and incidence of radio-graphic knee osteoarthritis (RKOA) in UK females: a prospective study. Arthritis Rheum 2009;60:2037-45.
70. Arendt-Nielsen L, Eskehave TN, Egsgaard LL, et al. Association between experimental pain biomarkers and serological markers in patients with different degree of painful knee osteoarthritis. Arthritis Rheumatol 2014; 66:3317-26.
71. Bos SD, Suchiman HE, Kloppenburg M, et al. Allelic variation at the C-reactive protein gene associates to both hand osteoarthritis severity and serum high sensitive C-reactive protein levels in the GARP study. Ann Rheum Dis 2008;67:877-9.
72. Kerkhof HJ, Bierma-Zeinstra SM, Castano-Betancourt MC, et al. Serum C reactive protein levels and genetic variation in the CRP gene are not associated with the prevalence, incidence or progression of osteo-arthritis independent of body mass index. Ann Rheum Dis 2010;69:1976-82.
73. Momiyama Y, Kawaguchi A, Kajiwara I, et al. Prognostic value of plasma high-sensitivity C-reactive protein levels in Japanese patients with stable coronary artery disease: the Japan NCVC-Collaborative Inflammation Cohort (JNIC) Study. Atherosclerosis 2009;207: 272-6.
74. Pfutzner A, Forst T. High-sensitivity C-reactive protein as cardiovascular risk marker in patients with diabetes mellitus. Diabetes Technol Ther 2006;8:28-36.
75. Ridker PM, Hennekens CH, Buring JE, et al. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000;342:836-43.
76. Danesh J, Kaptoge S, Mann AG, et al. Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med 2008;5:e78.
77. Kaptoge S, Seshasai SR, Gao P, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J 2014;35:578-89.
78. Ishikawa S, Kayaba K, Gotoh T, et al. Metabolic syndrome and C-reactive protein in the general population: JMS Cohort Study. Circ J 2007;71:26-31.
79. Santaniemi M, Ukkola O, Malo E, et al. Metabolic syndrome in the prediction of cardiovascular events: the potential additive role of hsCRP and adiponectin. Eur J Prev Cardiol 2014;21:1242-8.
80. Rabkin SW, Langer A, Ur E, et al. Inflammatory bio-markers CRP, MCP-1, serum amyloid alpha and interleukin-18 in patients with HTN and dyslipidemia: impact of diabetes mellitus on metabolic syndrome and the effect of statin therapy. Hypertens Res 2013;36: 550-8.
81. Rahman MM, Kopec JA, Anis AH, et al. Risk of cardiovascular disease in patients with osteoarthritis: a prospective longitudinal study. Arthritis Care Res (Hoboken) 2013;65:1951-8.
82. Clockaerts S, Van Osch GJ, Bastiaansen-Jenniskens YM, et al. Statin use is associated with reduced incidence and progression of knee osteoarthritis in the Rotterdam study. Ann Rheum Dis 2012;71:642-7.
83. Ramos R, Garcia-Gil M, Blanch J, et al. Statin use and onset of symptomatic knee osteoarthritis: a population-based cohort study. In: Poster presentation at the 2014 World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases (WCO). World Congress on Osteoporosis, Osteoarthritis, and Musculoskeletal Diseases (WCO), 2014.
84. Findlay DM. Vascular pathology and osteoarthritis. Rheumatology (Oxford) 2007;46:1763-8.
85. Pang J, Cao YL, Shi YY. [Subchondral bone in osteoarth-ritis: a review]. Zhongguo Gu Shang 2011;24:702-4.
86. Wen CY, Chen Y, Tang HL, et al. Bone loss at subchon-dral plate in knee osteoarthritis patients with hypertension and type 2 diabetes mellitus. Osteoarthritis Cartilage 2013;21:1716-23.
87. Horn CA, Bradley JD, Brandt KD, et al. Impairment of osteophyte formation in hyperglycemic patients with type II diabetes mellitus and knee osteoarthritis. Arthritis Rheum 1992;35:336-42.
88. Shin HY, Lee DC, Chu SH, et al. Chemerin levels are positively correlated with abdominal visceral fat accumulation. Clin Endocrinol (Oxf) 2012;77: 47-50.
89. Huang K, Du G, Li L, et al. Association of chemerin levels in synovial fluid with the severity of knee osteo-arthritis. Biomarkers 2012;17:16-20.
90. Fowler-Brown A, Kim DH, Shi L, et al. The Mediating Effect of Leptin on the Relationship Between Body Weight and Knee Osteoarthritis in Older Adults. Arthritis Rheumatol 2014.
91. Stannus OP, Cao Y, Antony B, et al. Cross-sectional and longitudinal associations between circulating leptin and knee cartilage thickness in older adults. Ann Rheum Dis 2013.
92. Karvonen-Gutierrez CA, Harlow SD, Mancuso P, et al. Association of leptin levels with radiographic knee osteoarthritis among a cohort of midlife women. Arthritis Care Res (Hoboken) 2013;65:936-44.
93. Van Spil WE, Welsing PM, Kloppenburg M, et al. Cross-sectional and predictive associations between plasma adipokines and radiographic signs of early-stage knee osteoarthritis: data from CHECK. Osteoarthritis Cartilage 2012;20:1278-85.
94. de Boer TN, van Spil WE, Huisman AM, et al. Serum adipokines in osteoarthritis;comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage. Osteoarthritis Cartilage 2012;20:846-53.
95. Perruccio AV, Mahomed NN, Chandran V, et al. Plasma adipokine levels and their association with overall burden of painful joints among individuals with hip and knee osteoarthritis. J Rheumatol 2014;41: 334-7.
96. Karvonen-Gutierrez CA, Harlow SD, Jacobson J, et al. The relationship between longitudinal serum leptin measures and measures of magnetic resonance imaging-assessed knee joint damage in a population of mid-life women. Ann Rheum Dis 2014;73:883-9.
97. Steppan CM, Lazar MA. Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 2002;13:18-23.
98. Yusuf E, Ioan-Facsinay A, Bijsterbosch J, et al. Association between leptin, adiponectin and resistin and long-term progression of hand osteoarthritis. Ann Rheum Dis 2011;70:1282-4.
99. Bas S, Finckh A, Puskas GJ, et al. Adipokines correlate with pain in lower limb osteoarthritis: different associations in hip and knee. Int Orthop 2014;38:2577-83.
100. Yusuf E, Ioan-Facsinay A, Bijsterbosch J, et al. Association between leptin, adiponectin and resistin and long-term progression of hand osteoarthritis. Ann Rheum Dis 2011;70:1282-4.
101. Massengale M, Lu B, Pan JJ, et al. Adipokine hormones and hand osteoarthritis: radiographic severity and pain. PLoS One 2012;7:e47860.
102. Massengale M, Reichmann WM, Losina E, et al. The relationship between hand osteoarthritis and serum leptin concentration in participants of the Third National Health and Nutrition Examination Survey. Arthritis Res Ther 2012;14:R132.
103. Choe JY, Bae J, Jung HY, et al. Serum resistin level is associated with radiographic changes in hand osteoarth-ritis: cross-sectional study. Joint Bone Spine 2012;79: 160-5.
104. Stannus OP, Jones G, Quinn SJ, et al. The association between leptin, interleukin-6, and hip radiographic osteoarthritis in older people: a cross-sectional study. Arthritis Res Ther 2010;12:R95.
105. Lubbeke A, Finckh A, Puskas GJ, et al. Do synovial leptin levels correlate with pain in end stage arthritis? Int Orthop 2013;37:2071-9.
106. Berry PA, Jones SW, Cicuttini FM, et al. Temporal relationship between serum adipokines, biomarkers of bone and cartilage turnover, and cartilage volume loss in a population with clinical knee osteoarthritis. Arthritis Rheum 2011;63:700-7.
107. Staikos C, Ververidis A, Drosos G, et al. The association of adipokine levels in plasma and synovial fluid with the severity of knee osteoarthritis. Rheumatology (Oxford) 2013;52:1077-83.
108. Ku JH, Lee CK, Joo BS, et al. Correlation of synovial fluid leptin concentrations with the severity of osteo-arthritis. Clin Rheumatol 2009;28:1431-5.
109. Laurberg TB, Frystyk J, Ellingsen T, et al. Plasma adipo-nectin in patients with active, early, and chronic rheumatoid arthritis who are steroid-and disease-modifying antirheumatic drug-naive compared with patients with osteoarthritis and controls. J Rheumatol 2009;36:1885-91.
110. Honsawek S, Chayanupatkul M. Correlation of plasma and synovial fluid adiponectin with knee osteoarthritis severity. Arch Med Res 2010;41:593-8.
111. van Spil WE, Jansen NW, Bijlsma JW, et al. Clusters within a wide spectrum of biochemical markers for osteoarthritis: data from CHECK, a large cohort of individuals with very early symptomatic osteoarthritis. Osteoarthritis Cartilage 2012;20:745-54.
112. Koskinen A, Vuolteenaho K. Leptin enhances MMP-l, MMP-3 and MMP-13 production in human osteoarth-ritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clin Exp Rheumatol 2011;29:57-64.
113. Duan Y, Hao D, Li M, et al. Increased synovial fluid visfatin is positively linked to cartilage degradation bio-markers in osteoarthritis. Rheumatol Int 2012;32: 985-90.
114. Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, et al. Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 2003;88:5452-5.
115. Griffin TM, Huebner JL, Kraus VB, et al. Induction of osteoarthritis and metabolic inflammation by a very high-fat diet in mice: effects of short-term exercise. Arthritis Rheum 2012;64:443-53.
116. Griffin TM, Fermor B, Huebner JL, et al. Diet-induced obesity differentially regulates behavioral, biomechan-ical, and molecular risk factors for osteoarthritis in mice. Arthritis Res Ther 2010;12:R130.
117. Figenschau Y, Knutsen G, Shahazeydi S, et al. Human articular chondrocytes express functional leptin receptors. Biochem Biophys Res Commun 2001;287:190-7.
118. Griffin TM, Huebner JL, Kraus VB, et al. Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum 2009;60: 2935-44.
119. Mark AL, Shaffer RA, Correia ML, et al. Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice. J Hypertens 1999;17:1949-53.
120. Koskinen A, Vuolteenaho K, Nieminen R, et al. Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clin Exp Rheumatol 2011;29:57-64.
121. Berg V, Sveinbjornsson B, Bendiksen S, et al. Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin(21-157). Arthritis Res Ther 2010;12:R228.
122. Carbone F, La Rocca C, Matarese G. Immunological functions of leptin and adiponectin. Biochimie 2012;94: 2082-8.
123. Aktas E, Sener E, Gocun PU. Mechanically induced experimental knee osteoarthritis benefits from anti-inflammatory and immunomodulatory properties of sim-vastatin via inhibition of matrix metalloproteinase-3. J Orthop Traumatol 2011;12:145-51.
124. Szotowska M, Czerwienska B, Adamczak M, et al. Effect of low-dose atorvastatin on plasma concentrations of adipokines in patients with metabolic syndrome. Kidney Blood Press Res 2012;35:226-32.