Adipokines as drug targets in joint and bone disease

Drug Discovery Today

Volumn 19, Issue 3, 2014, Pages 241-258

  Scotece, Morena ^a   Conde, Javier ^a   Vuolteenaho, Katriina ^b   Koskinen, Anna ^b   López, Veronica ^a   Gómez Reino, Juan ^a   Lago, Francisca ^a   Moilanen, Eeva ^b   Gualillo, Oreste ^a  

^a Santiago University Clinical Hospital   (Spain)

^b TAMPERE UNIVERSITY OF TECHNOLOGY   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; ADIPONECTIN RECEPTOR; APELIN; CHEMERIN; COMPLEMENT FACTOR D; LEPTIN; LEPTIN RECEPTOR; NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; RESISTIN; VASPIN;

ARTHROPATHY; AUTOIMMUNE DISEASE; BONE DISEASE; CARTILAGE; DRUG TARGETING; HUMAN; INFLAMMATION; INFLAMMATORY DISEASE; METABOLIC DISORDER; MUSCULOSKELETAL SYSTEM; NONHUMAN; OBESITY; OSTEOARTHRITIS; OSTEOPOROSIS; PATHOGENESIS; PLEIOTROPY; PROTEIN FUNCTION; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SYNOVIUM; WHITE ADIPOSE TISSUE; ANIMAL; BONE DISEASES; DRUG DESIGN; JOINT DISEASES; METABOLISM; MOLECULARLY TARGETED THERAPY; PATHOPHYSIOLOGY;

ADIPOKINES; ADIPOSE TISSUE, WHITE; ANIMALS; BONE DISEASES; DRUG DESIGN; HUMANS; INFLAMMATION; JOINT DISEASES; MOLECULAR TARGETED THERAPY; OBESITY;

EID: 84896402811     PISSN: 13596446     EISSN: 18785832     Source Type: Journal    
DOI: 10.1016/j.drudis.2013.07.012     Document Type: Review

References (248)

1. M.F. Gregor, and G.S. Hotamisligil Inflammatory mechanisms in obesity Annu. Rev. Immunol. 29 2011 415 445
2. N. Ouchi et al. Adipokines in inflammation and metabolic disease Nat. Rev. Immunol. 11 2011 85 97
3. R. Gomez et al. What's new in our understanding of the role of adipokines in rheumatic diseases? Nat. Rev. Rheumatol. 7 2011 528 536
4. A. Tarkowski et al. Resistin competes with lipopolysaccharide for binding to toll-like receptor 4 J. Cell. Mol. Med. 14 2010 1419 1431
5. Y. Zhang et al. Positional cloning of the mouse obese gene and its human homologue Nature 372 1994 425 432 (Pubitemid 24365442)
6. R.S. Ahima, and J.S. Flier Adipose tissue as an endocrine organ Trends Endocrinol. Metab. 11 2000 327 332
7. H. Dumond et al. Evidence for a key role of leptin in osteoarthritis Arthritis Rheum. 48 2003 3118 3129 (Pubitemid 37409323)
8. M. Morroni et al. In vivo leptin expression in cartilage and bone cells of growing rats and adult humans J. Anat. 205 2004 291 296 (Pubitemid 39406156)
9. N. Presle et al. Differential distribution of adipokines between serum and synovial fluid in patients with osteoarthritis. Contribution of joint tissues to their articular production Osteoarthritis Cartilage 14 2006 690 695 (Pubitemid 43842733)
10. T. Simopoulou et al. Differential expression of leptin and leptin's receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism Osteoarthritis Cartilage 15 2007 872 883 (Pubitemid 47209251)
11. D. Iliopoulos et al. Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention Ann. Rheum. Dis. 66 2007 1616 1621 (Pubitemid 350205450)
12. K. Jarvinen et al. Selective iNOS inhibitor 1400W enhances anti-catabolic IL-10 and reduces destructive MMP-10 in OA cartilage, Survey of the effects of 1400W on inflammatory mediators produced by OA cartilage as detected by protein antibody array Clin. Exp. Rheumatol. 26 2008 275 282 (Pubitemid 351659134)
13. E.D. Green et al. The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7 Genome Res. 5 1995 5 12
14. Y. Chilliard et al. Leptin in ruminants. Gene expression in adipose tissue and mammary gland, and regulation of plasma concentration Domest. Anim. Endocrinol. 21 2001 271 295 (Pubitemid 34204089)
15. M. Otero et al. Changes in plasma levels of fat-derived hormones adiponectin, leptin, resistin and visfatin in patients with rheumatoid arthritis Ann. Rheum. Dis. 65 2006 1198 1201 (Pubitemid 44277396)
16. M.K. Sinha et al. Ultradian oscillations of leptin secretion in humans Biochem. Biophys. Res. Commun. 228 1996 733 738 (Pubitemid 26421447)
17. N. Ghilardi, and R.C. Skoda The leptin receptor activates janus kinase 2 and signals for proliferation in a factor-dependent cell line Mol. Endocrinol. 11 1997 393 399 (Pubitemid 27147006)
18. G. Bahrenberg et al. Identification of the critical sequence elements in the cytoplasmic domain of leptin receptor isoforms required for Janus kinase/signal transducer and activator of transcription activation by receptor heterodimers Mol. Endocrinol. 16 2002 859 872 (Pubitemid 34297753)
19. D.W. White et al. Leptin receptor (OB-R) signaling. Cytoplasmic domain mutational analysis and evidence for receptor homo-oligomerization J. Biol. Chem. 272 1997 4065 4071 (Pubitemid 27078469)
20. R. Devos et al. Ligand-independent dimerization of the extracellular domain of the leptin receptor and determination of the stoichiometry of leptin binding J. Biol. Chem. 272 1997 18304 18310 (Pubitemid 27306421)
21. A.S. Banks et al. Activation of downstream signals by the long form of the leptin receptor J. Biol. Chem. 275 2000 14563 14572 (Pubitemid 30339746)
22. C. Bjorbaek et al. Divergent signaling capacities of the long and short isoforms of the leptin receptor J. Biol. Chem. 272 1997 32686 32695 (Pubitemid 28011961)
23. O. Gualillo et al. Leptin promotes the tyrosine phosphorylation of SHC proteins and SHC association with GRB2 Mol. Cell. Endocrinol. 190 2002 83 89 (Pubitemid 34462054)
24. K.D. Niswender et al. Intracellular signalling. Key enzyme in leptin-induced anorexia Nature 413 2001 794 795 (Pubitemid 33026839)
25. K. Vuolteenaho et al. Leptin enhances synthesis of proinflammatory mediators in human osteoarthritic cartilage - mediator role of NO in leptin-induced PGE2, IL-6, and IL-8 production Mediators Inflamm. 2009 2009 345838
26. Y. Akasaka et al. Direct evidence for leptin-induced lipid oxidation independent of long-form leptin receptor Biochim. Biophys. Acta 1801 2010 1115 1122
27. B.F. Belgardt et al. PDK1 deficiency in POMC-expressing cells reveals FOXO1-dependent and -independent pathways in control of energy homeostasis and stress response Cell. Metab. 7 2008 291 301 (Pubitemid 351467391)
28. A. Oswal, and G. Yeo Leptin and the control of body weight: a review of its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity Obesity (Silver Spring) 18 2010 221 229
29. A. Koskinen 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. 29 2011 57 64
30. H. Munzberg et al. Leptin receptor action and mechanisms of leptin resistance Cell. Mol. Life Sci. 62 2005 642 652
31. R. Coppari, and C. Bjorbaek Leptin revisited: its mechanism of action and potential for treating diabetes Nat. Rev. Drug Discov. 11 2012 692 708
32. S. Pallu et al. Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis Arthritis Res. Ther. 12 2010 R112
33. K. Vuolteenaho et al. Leptin levels are increased and its negative regulators, SOCS-3 and sOb-R are decreased in obese patients with osteoarthritis: a link between obesity and osteoarthritis Ann. Rheum. Dis. 71 2012 1912 1913
34. A. Koskinen, K. Vuolteenaho, R. Korhonen, T. Moilanen, and E. Moilanen Suppressor of cytokine signaling 3 is reduced in obese patients with osteoarthritis and regulates leptin responses in chondrocytes Arthritis Rheum. 64 2012 S1064
35. J. Gallagher et al. The infrapatellar fat pad: anatomy and clinical correlations Knee Surg. Sports Traumatol. Arthrosc. 13 2005 268 272 (Pubitemid 41217968)
36. E. Distel et al. The infrapatellar fat pad in knee osteoarthritis: an important source of interleukin-6 and its soluble receptor Arthritis Rheum. 60 2009 3374 3377
37. W. Hui et al. Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases Ann. Rheum. Dis. 71 2012 455 462
38. S. Clockaerts et al. Cytokine production by infrapatellar fat pad can be stimulated by interleukin 1beta and inhibited by peroxisome proliferator activated receptor alpha agonist Ann. Rheum. Dis. 71 2012 1012 1018
39. Y.M. Bastiaansen-Jenniskens et al. Infrapatellar fat pad of patients with end-stage osteoarthritis inhibits catabolic mediators in cartilage Ann. Rheum. Dis. 71 2012 288 294
40. I.R. Reid Fat and bone Arch. Biochem. Biophys. 503 2010 20 27
41. J. Gomez-Ambrosi et al. The bone-adipose axis in obesity and weight loss Obes. Surg. 18 2008 1134 1143
42. P. Ducy et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass Cell 100 2000 197 207 (Pubitemid 30064908)
43. S. Takeda et al. Leptin regulates bone formation via the sympathetic nervous system Cell 111 2002 305 317 (Pubitemid 35345151)
44. F. Elefteriou et al. Leptin regulation of bone resorption by the sympathetic nervous system and CART Nature 434 2005 514 520 (Pubitemid 40477060)
45. N. Balthasar et al. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis Neuron 42 2004 983 991 (Pubitemid 38798236)
46. P. Pogoda et al. Leptin inhibits bone formation not only in rodents, but also in sheep J. Bone Miner. Res. 21 2006 1591 1599 (Pubitemid 44484604)
47. F.T. Beil et al. Effects of increased bone formation on fracture healing in mice J. Trauma 70 2011 857 862
48. C.M. Steppan et al. Leptin is a potent stimulator of bone growth in ob/ob mice Regul. Pept. 92 2000 73 78
49. J. Cornish et al. Leptin directly regulates bone cell function in vitro and reduces bone fragility in vivo J. Endocrinol. 175 2002 405 415 (Pubitemid 35414387)
50. K.J. Motyl, and C.J. Rosen Understanding leptin-dependent regulation of skeletal homeostasis Biochimie 94 2012 2089 2096
51. Y. Figenschau et al. Human articular chondrocytes express functional leptin receptors Biochem. Biophys. Res. Commun. 287 2001 190 197 (Pubitemid 32912482)
52. M. Otero et al. Synergistic induction of nitric oxide synthase type II: in vitro effect of leptin and interferon-gamma in human chondrocytes and ATDC5 chondrogenic cells Arthritis Rheum. 48 2003 404 409 (Pubitemid 36278009)
53. M. Otero et al. Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1 Arthritis Res. Ther. 7 2005 R581 R591
54. R. Gomez et al. Adiponectin and leptin increase IL-8 production in human chondrocytes Ann. Rheum. Dis. 70 2011 2052 2054
55. M. Otero et al. Phosphatidylinositol 3-kinase, MEK-1 and p38 mediate leptin/interferon-gamma synergistic NOS type II induction in chondrocytes Life Sci. 81 2007 1452 1460 (Pubitemid 350018780)
56. J. Conde et al. Adiponectin and leptin induce VCAM-1 expression in human and murine chondrocytes PLoS ONE 7 2012 e52533
57. X.F. Li et al. Stage specific effect of leptin on the expressions of estrogen receptor and extracellular matrix in a model of chondrocyte differentiation Cytokine 61 2013 876 884
58. L. Wang et al. Leptin antagonizes peroxisome proliferator-activated receptor-gamma signaling in growth plate chondrocytes PPAR Res. 2012 2012 756198
59. J. Liang et al. Leptin-mediated cytoskeletal remodeling in chondrocytes occurs via the RhoA/ROCK pathway J. Orthop. Res. 29 2011 369 374
60. M. Ben-Eliezer et al. Leptin regulates chondrogenic differentiation in ATDC5 cell-line through JAK/STAT and MAPK pathways Endocrine 32 2007 235 244
61. Y. Kishida et al. Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification Bone 37 2005 607 621 (Pubitemid 41476383)
62. K.M. Tong et al. Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-kappaB/p300 binding in human synovial fibroblasts Cell Signal. 20 2008 1478 1488
63. S. Muraoka et al. Leptin stimulates interleukin-6 production via janus kinase 2/signal transducer and activator of transcription 3 in rheumatoid synovial fibroblasts Clin. Exp. Rheumatol. 31 2013 589 595
64. S.Q. Liu et al. Serum leptin level and its association with bone mineral density in obese children Zhongguo Dang Dai Er Ke Za Zhi 11 2009 745 748
65. I.R. Reid Obesity and osteoporosis Ann. Endocrinol. (Paris) 67 2006 125 129
66. H.G. Silva et al. Influence of obesity on bone density in postmenopausal women Arq. Bras. Endocrinol. Metabol. 51 2007 943 949
67. C. Albala et al. Obesity as a protective factor for postmenopausal osteoporosis Int. J. Obes. Relat. Metab. Disord. 20 1996 1027 1032 (Pubitemid 26366457)
68. L.J. Zhao et al. Relationship of obesity with osteoporosis J. Clin. Endocrinol. Metab. 92 2007 1640 1646
69. L.J. Zhao et al. Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis J. Bone Miner. Res. 23 2008 17 29
70. Y. Shi et al. Dissociation of the neuronal regulation of bone mass and energy metabolism by leptin in vivo Proc. Natl. Acad. Sci. U. S. A. 105 2008 20529 20533
71. Y. Fujita et al. Serum leptin levels negatively correlate with trabecular bone mineral density in high-fat diet-induced obesity mice J. Musculoskelet. Neuronal Interact. 12 2012 84 94
72. A. Fisher et al. Interactions between serum adipokines and osteocalcin in older patients with hip fracture Int. J. Endocrinol. 2012 2012 684323
73. E. Toussirot et al. Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis Metabolism 56 2007 1383 1389 (Pubitemid 47404601)
74. M.S. Mutabaruka et al. Local leptin production in osteoarthritis subchondral osteoblasts may be responsible for their abnormal phenotypic expression Arthritis Res. Ther. 12 2010 R20
75. A. Schaffler et al. Adipocytokines in synovial fluid JAMA 290 2003 1709 1710
76. J.H. Ku et al. Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis Clin. Rheumatol. 28 2009 1431 1435
77. C.A. Karvonen-Gutierrez et al. Leptin levels are associated with radiographic knee osteoarthritis among a cohort of mid-life women Arthritis Care Res. (Hoboken) 65 2013 936 944
78. T.M. Griffin et al. Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis Arthritis Rheum. 60 2009 2935 2944
79. T.N. de Boer et al. Serum adipokines in osteoarthritis; comparison with controls and relationship with local parameters of synovial inflammation and cartilage damage Osteoarthritis Cartilage 20 2012 846 853
80. S.A. Oliveria et al. Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee Epidemiology 10 1999 161 166 (Pubitemid 29093953)
81. E. Yusuf et al. Association between weight or body mass index and hand osteoarthritis: a systematic review Ann. Rheum. Dis. 69 2011 761 765
82. M. Massengale et al. Adipokine hormones and hand osteoarthritis: radiographic severity and pain PLoS ONE 7 2012 e47860
83. E. Yusuf et al. Association between leptin, adiponectin and resistin and long-term progression of hand osteoarthritis Ann. Rheum. Dis. 70 2010 1282 1284
84. S.W. Lee et al. Measurement of the serum leptin level could assist disease activity monitoring in rheumatoid arthritis Rheumatol. Int. 27 2007 537 540
85. B. Targonska-Stepniak et al. Leptin serum levels in rheumatoid arthritis patients: relation to disease duration and activity Rheumatol. Int. 28 2008 585 591 (Pubitemid 351422621)
86. B. Targonska-Stepniak et al. Adiponectin and leptin serum concentrations in patients with rheumatoid arthritis Rheumatol. Int. 30 2010 731 737
87. S.M. Olama et al. Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and erosion Rheumatol. Int. 32 2012 683 690
88. Y.H. Rho et al. Adipocytokines are associated with radiographic joint damage in rheumatoid arthritis Arthritis Rheum. 60 2009 1906 1914
89. C. Procaccini et al. An oscillatory switch in mTOR kinase activity sets regulatory T cell responsiveness Immunity 33 2011 929 941
90. C.A. Notley, and M.R. Ehrenstein The yin and yang of regulatory T cells and inflammation in RA Nat. Rev. Rheumatol. 6 2010 572 577
91. V. De Rosa et al. A key role of leptin in the control of regulatory T cell proliferation Immunity 26 2007 241 255 (Pubitemid 46329441)
92. E. Moilanen et al. Increased adipsin and low leptin levels are associated with higher remission rates in early RA patients treated with a combination of DMARDs (NEO-RACo study) Arthritis Rheum. 58 2008 S772 (Abstr. 1639)
93. T. Kadowaki, and T. Yamauchi Adiponectin and adiponectin receptors Endocr. Rev. 26 2005 439 451 (Pubitemid 40686653)
94. D.K. Oh et al. Adiponectin in health and disease Diabetes Obes. Metab. 9 2007 282 289 (Pubitemid 46502045)
95. M. Stumvoll et al. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes Diabetes 51 2002 37 41 (Pubitemid 34517977)
96. J.P. Whitehead et al. Adiponectin - a key adipokine in the metabolic syndrome Diabetes Obes. Metab. 8 2006 264 280
97. N. Maeda et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein Diabetes 50 2001 2094 2099 (Pubitemid 33643677)
98. T. Yamauchi et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions Nat. Med. 13 2007 332 339 (Pubitemid 46376688)
99. T. Yamauchi et al. Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice Nat. Genet. 30 2002 221 226
100. A.R. Nawrocki et al. Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferator-activated receptor gamma agonists J. Biol. Chem. 281 2006 2654 2660 (Pubitemid 43845727)
101. T. Kadowaki, and T. Yamauchi Adiponectin receptor signaling: a new layer to the current model Cell. Metab. 13 2011 123 124
102. A. Koskinen et al. Adiponectin associates with markers of cartilage degradation in osteoarthritis and induces production of proinflammatory and catabolic factors through mitogen-activated protein kinase pathways Arthritis Res. Ther. 13 2011 R184
103. I.R. Klein-Wieringa et al. The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype Ann. Rheum. Dis. 70 2011 851 857
104. R. Gandhi et al. Microarray analysis of the infrapatellar fat pad in knee osteoarthritis: relationship with joint inflammation J. Rheumatol. 38 2011 1966 1972
105. K. Oshima et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast Biochem. Biophys. Res. Commun. 331 2005 520 526 (Pubitemid 40602668)
106. Y. Shinoda et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways J. Cell. Biochem. 99 2006 196 208 (Pubitemid 44297964)
107. H.S. Berner et al. Adiponectin and its receptors are expressed in bone-forming cells Bone 35 2004 842 849 (Pubitemid 39349215)
108. X.H. Luo et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway Exp. Cell. Res. 309 2005 99 109
109. I. Kanazawa Adiponectin in metabolic bone disease Curr. Med. Chem. 19 2009 5481 5492
110. X.H. Luo et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts through the MAPK signaling pathway J. Bone Miner. Res. 21 2006 1648 1656
111. Y. Wang et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner J. Biol. Chem. 280 2005 18341 18347 (Pubitemid 41389081)
112. C.Y. Huang et al. Adiponectin increases BMP-2 expression in osteoblasts via AdipoR receptor signaling pathway J. Cell. Physiol. 224 2010 475 483
113. G.A. Williams et al. In vitro and in vivo effects of adiponectin on bone Endocrinology 150 2009 3603 3610
114. T.H. Chen et al. Evidence for a protective role for adiponectin in osteoarthritis Biochim. Biophys. Acta 1762 2006 711 718
115. R. Lago et al. A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes Osteoarthritis Cartilage 16 2008 1101 1109
116. T.D. Challa et al. Effect of adiponectin on ATDC5 proliferation, differentiation and signaling pathways Mol. Cell. Endocrinol. 323 2010 282 291
117. E.H. Kang et al. Adiponectin is a potential catabolic mediator in osteoarthritis cartilage Arthritis Res. Ther. 12 2010 R231
118. K.M. Tong et al. Adiponectin increases MMP-3 expression in human chondrocytes through AdipoR1 signaling pathway J. Cell. Biochem. 112 2011 1431 1440
119. A. Ehling et al. The potential of adiponectin in driving arthritis J. Immunol. 176 2006 4468 4478 (Pubitemid 44264427)
120. N. Kusunoki et al. Adiponectin stimulates prostaglandin E(2) production in rheumatoid arthritis synovial fibroblasts Arthritis Rheum. 62 2010 1641 1649
121. L. Lenchik et al. Adiponectin as a novel determinant of bone mineral density and visceral fat Bone 33 2003 646 651 (Pubitemid 37222391)
122. E. Biver et al. Influence of adipokines and ghrelin on bone mineral density and fracture risk: a systematic review and meta-analysis J. Clin. Endocrinol. Metab. 96 2011 2703 2713
123. L. Basurto et al. Adiponectin is associated with low bone mineral density in elderly men Eur. J. Endocrinol. 160 2009 289 293
124. M. Frost et al. Adiponectin and peak bone mass in men: a cross-sectional, population-based study Calcif. Tissue Int. 87 2010 36 43
125. I. Kanazawa et al. Relationships between serum adiponectin levels versus bone mineral density, bone metabolic markers, and vertebral fractures in type 2 diabetes mellitus Eur. J. Endocrinol. 160 2009 265 273
126. K. Michaelsson et al. Serum adiponectin in elderly men does not correlate with fracture risk J. Clin. Endocrinol. Metab. 93 2008 4041 4047
127. I. Kanazawa et al. Baseline serum total adiponectin level is positively associated with changes in bone mineral density after 1-year treatment of type 2 diabetes mellitus Metabolism 59 2010 1252 1256
128. G.A. King et al. Relationship between leptin, adiponectin, bone mineral density, and measures of adiposity among pre-menopausal Hispanic and Caucasian women Endocr. Res. 35 2010 106 117
129. S. Okuno et al. Serum adiponectin and bone mineral density in male hemodialysis patients Osteoporos. Int. 23 2012 2027 2035
130. T.B. Laurberg et al. Plasma adiponectin 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. 36 2009 1885 1891
131. M. Filkova et al. Increased serum adiponectin levels in female patients with erosive compared with non-erosive osteoarthritis Ann. Rheum. Dis. 68 2009 295 296
132. R. Gandhi et al. Relationship between body habitus and joint leptin levels in a knee osteoarthritis population J. Orthop. Res. 28 2011 329 333
133. M. Matsubara et al. Decreased plasma adiponectin concentrations in women with low-grade C-reactive protein elevation Eur. J. Endocrinol. 148 2003 657 662 (Pubitemid 36758296)
134. M. Matsubara et al. Decreased plasma adiponectin concentrations in nondiabetic women with elevated homeostasis model assessment ratios Eur. J. Endocrinol. 148 2003 343 350 (Pubitemid 36410720)
135. K. Ebina et al. Serum adiponectin concentrations correlate with severity of rheumatoid arthritis evaluated by extent of joint destruction Clin. Rheumatol. 28 2009 445 451
136. D. Hao et al. Synovial fluid level of adiponectin correlated with levels of aggrecan degradation markers in osteoarthritis Rheumatol. Int. 31 2011 1433 1437
137. K. Uchida et al. Hyperlipidemia and hyperinsulinemia in the spontaneous osteoarthritis mouse model STR/Ort. Exp. Anim. 58 2009 181 187
138. S. Honsawek, and M. Chayanupatkul Correlation of plasma and synovial fluid adiponectin with knee osteoarthritis severity Arch. Med. Res. 41 2010 593 598
139. E.A. Alkady et al. [Serum and synovial adiponectin, resistin, and visfatin levels in rheumatoid arthritis patients. Relation to disease activity] Z. Rheumatol. 70 2011 602 608
140. I.R. Klein-Wieringa et al. Baseline serum adipokine levels predict radiographic progression in early rheumatoid arthritis Arthritis Rheum. 63 2011 2567 2574
141. J.T. Giles et al. Adiponectin is a mediator of the inverse association of adiposity with radiographic damage in rheumatoid arthritis Arthritis Rheum. 61 2009 1248 1256
142. Y.A. Lee et al. Synergy between adiponectin and interleukin-1beta on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes Exp. Mol. Med. 44 2012 440 447
143. H.M. Choi et al. Adiponectin may contribute to synovitis and joint destruction in rheumatoid arthritis by stimulating vascular endothelial growth factor, matrix metalloproteinase-1, and matrix metalloproteinase-13 expression in fibroblast-like synoviocytes more than proinflammatory mediators Arthritis Res. Ther. 11 2009 R161
144. K.W. Frommer et al. Adiponectin-mediated changes in effector cells involved in the pathophysiology of rheumatoid arthritis Arthritis Rheum. 62 2010 2886 2899
145. K.W. Frommer et al. Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis? Ann. Rheum. Dis. 71 2012 1724 1732
146. B. Samal et al. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor Mol. Cell. Biol. 14 1994 1431 1437
147. A. Fukuhara et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin Science 307 2005 426 430 (Pubitemid 40139988)
148. D. Friebe et al. Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans Diabetologia 54 2011 1200 1211
149. V. Catalan et al. Association of increased visfatin/PBEF/NAMPT circulating concentrations and gene expression levels in peripheral blood cells with lipid metabolism and fatty liver in human morbid obesity Nutr. Metab. Cardiovasc. Dis. 21 2011 245 253
150. C.A. Curat et al. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin Diabetologia 49 2006 744 747 (Pubitemid 43357549)
151. A. Fukuhara et al. Retraction Science 318 2007 565
152. S.H. Jia et al. Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis J. Clin. Invest. 113 2004 1318 1327 (Pubitemid 39069931)
153. A.R. Moschen et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties J. Immunol. 178 2007 1748 1758 (Pubitemid 46154646)
154. H. Xie et al. Insulin-like effects of visfatin on human osteoblasts Calcif. Tissue Int. 80 2007 201 210 (Pubitemid 46411878)
155. C. Jacques et al. Proinflammatory actions of visfatin/nicotinamide phosphoribosyltransferase (Nampt) involve regulation of insulin signaling pathway and Nampt enzymatic activity J. Biol. Chem. 287 2012 15100 15108
156. R.R. Yammani, and R.F. Loeser Extracellular nicotinamide phosphoribosyltransferase (NAMPT/visfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes Arthritis Res. Ther. 14 2012 R23
157. X.D. Peng et al. Relationships between serum adiponectin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in Chinese men Clin. Chim. Acta 387 2008 31 35
158. H. Zhang et al. Relationships between serum adiponectin, apelin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in post-menopausal Chinese women J. Endocrinol. Invest. 33 2010 707 711
159. R. Gruodyte et al. Adipocytokines and bone mineral density in adolescent female athletes Acta Paediatr. 99 2010 1879 1884
160. G. Iacobellis et al. Relation of adiponectin, visfatin and bone mineral density in patients with metabolic syndrome J. Endocrinol. Invest. 34 2011 e12 e15
161. N. Sucunza et al. A link between bone mineral density and serum adiponectin and visfatin levels in acromegaly J. Clin. Endocrinol. Metab. 94 2009 3889 3896
162. B. Cillero-Pastor et al. Proteomic analysis by two-dimensional electrophoresis to identify the normal human chondrocyte proteome stimulated by tumor necrosis factor alpha and interleukin-1beta Arthritis Rheum. 62 2010 802 814
163. M. Gosset et al. Crucial role of visfatin/pre-B cell colony-enhancing factor in matrix degradation and prostaglandin E2 synthesis in chondrocytes: possible influence on osteoarthritis Arthritis Rheum. 58 2008 1399 1409 (Pubitemid 351705929)
164. K. Chauffier et al. Induction of the chemokine il-8/kc by the articular cartilage: possible influence on osteoarthritis Joint Bone Spine 79 2012 604 609
165. A.L. McNulty et al. The effects of adipokines on cartilage and meniscus catabolism Connect. Tissue Res. 52 2011 523 533
166. F. Brentano et al. Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities Arthritis Rheum. 56 2007 2829 2839 (Pubitemid 47502729)
167. F.M. Meier et al. Visfatin/pre-B-cell colony-enhancing factor (PBEF), a proinflammatory and cell motility-changing factor in rheumatoid arthritis J. Biol. Chem. 287 2012 28378 28385
168. M. Tohidi et al. Omentin-1, visfatin and adiponectin levels in relation to bone mineral density in Iranian postmenopausal women Bone 51 2012 876 881
169. Y. Li et al. Nicotinamide phosphoribosyltransferase (Nampt) affects the lineage fate determination of mesenchymal stem cells: a possible cause for reduced osteogenesis and increased adipogenesis in older individuals J. Bone Miner. Res. 26 2011 2656 2664
170. A.R. Moschen et al. Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation-related bone disease Mutat. Res. 690 2010 95 101
171. Y. Duan et al. Increased synovial fluid visfatin is positively linked to cartilage degradation biomarkers in osteoarthritis Rheumatol. Int. 32 2012 985 990
172. W.P. Chen et al. Increased serum concentrations of visfatin and its production by different joint tissues in patients with osteoarthritis Clin. Chem. Lab. Med. 48 2010 1141 1145
173. M.A. Nowell et al. Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis Arthritis Rheum. 54 2006 2084 2095 (Pubitemid 44051064)
174. N. Busso et al. Pharmacological inhibition of nicotinamide phosphoribosyltransferase/visfatin enzymatic activity identifies a new inflammatory pathway linked to NAD PLoS ONE 3 2008 e2267
175. J. Jurcovicova et al. Alterations in adipocyte glucose transporter GLUT4 and circulating adiponectin and visfatin in rat adjuvant induced arthritis Gen. Physiol. Biophys. 29 2010 79 84
176. L. Evans et al. Suppression of leukocyte infiltration and cartilage degradation by selective inhibition of pre-B cell colony-enhancing factor/visfatin/nicotinamide phosphoribosyltransferase: Apo866-mediated therapy in human fibroblasts and murine collagen-induced arthritis Arthritis Rheum. 63 2011 1866 1877
177. L. Senolt et al. The level of serum visfatin (PBEF) is associated with total number of B cells in patients with rheumatoid arthritis and decreases following B cell depletion therapy Cytokine 55 2011 116 121
178. H. Matsui et al. Visfatin (pre-B cell colony-enhancing factor) gene expression in patients with rheumatoid arthritis Ann. Rheum. Dis. 67 2008 571 572 (Pubitemid 351498444)
179. M.A. Gonzalez-Gay et al. Visfatin is not associated with inflammation or metabolic syndrome in patients with severe rheumatoid arthritis undergoing anti-TNF-alpha therapy Clin. Exp. Rheumatol. 28 2010 56 62
180. R. Klaasen et al. Treatment-specific changes in circulating adipocytokines: a comparison between tumour necrosis factor blockade and glucocorticoid treatment for rheumatoid arthritis Ann. Rheum. Dis. 71 2012 1510 1516
181. C.M. Steppan et al. A family of tissue-specific resistin-like molecules Proc. Natl. Acad. Sci. U. S. A. 98 2001 502 506 (Pubitemid 32105071)
182. S. Ghosh et al. The genomic organization of mouse resistin reveals major differences from the human resistin: functional implications Gene 305 2003 27 34 (Pubitemid 36197863)
183. L. Patel et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators Biochem. Biophys. Res. Commun. 300 2003 472 476 (Pubitemid 38375833)
184. J.N. Fain et al. Resistin release by human adipose tissue explants in primary culture Biochem. Biophys. Res. Commun. 300 2003 674 678 (Pubitemid 36268889)
185. M.W. Rajala et al. Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production J. Clin. Invest. 111 2003 225 230 (Pubitemid 36105921)
186. H. Satoh et al. Adenovirus-mediated chronic "hyper- resistinemia" leads to in vivo insulin resistance in normal rats J. Clin. Invest. 114 2004 224 231 (Pubitemid 39071627)
187. K.H. Kim et al. Dominant inhibitory adipocyte-specific secretory factor (ADSF)/resistin enhances adipogenesis and improves insulin sensitivity Proc. Natl. Acad. Sci. U. S. A. 101 2004 6780 6785
188. D.R. Schwartz, and M.A. Lazar Human resistin: found in translation from mouse to man Trends Endocrinol. Metab. 22 2011 259 265
189. A.M. Kunnari et al. The expression of human resistin in different leucocyte lineages is modulated by LPS and TNFalpha Regul. Pept. 157 2009 57 63
190. M. Lehrke et al. An inflammatory cascade leading to hyperresistinemia in humans PLoS Med. 1 2004 e45
191. C.M. Steppan et al. Activation of SOCS-3 by resistin Mol. Cell. Biol. 25 2005 1569 1575 (Pubitemid 40204931)
192. M. Pirvulescu et al. A novel pro-inflammatory mechanism of action of resistin in human endothelial cells: up-regulation of SOCS3 expression through STAT3 activation Biochem. Biophys. Res. Commun. 422 2012 321 326
193. R.R. Banerjee et al. Regulation of fasted blood glucose by resistin Science 303 2004 1195 1198 (Pubitemid 38233585)
194. L. Thommesen et al. Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism J. Cell. Biochem. 99 2006 824 834 (Pubitemid 44522000)
195. S.F. Vondracek et al. The relationship between adipokines, body composition, and bone density in men with chronic obstructive pulmonary disease Int. J. Chron. Obstruct. Pulmon. Dis. 4 2009 267 277
196. K.W. Oh et al. The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men Clin. Endocrinol. (Oxf.) 63 2005 131 138 (Pubitemid 41097980)
197. A. Fisher et al. Serum resistin in older patients with hip fracture: relationship with comorbidity and biochemical determinants of bone metabolism Cytokine 56 2011 157 166
198. J.H. Lee et al. Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in vitro Osteoarthritis Cartilage 17 2009 613 620
199. L. Senolt et al. Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum Ann. Rheum. Dis. 66 2007 458 463 (Pubitemid 46580464)
200. P.A. Berry 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. 63 2011 700 707
201. J.Y. Choe et al. Serum resistin level is associated with radiographic changes in hand osteoarthritis: cross-sectional study Joint Bone Spine 79 2012 160 165
202. A. Koskinen, K. Vuolteenaho, R. Nieminen, T. Moilanen, and E. Moilanen Association of adipokines adipsin, resistin and leptin with interleukin-6 and metalloproteinases-1 and -3 in synovial fluid from osteoarthritis patients Scand. J. Rheumatol. 41 2012 327
203. T. Yoshino et al. Elevated serum levels of resistin, leptin, and adiponectin are associated with C-reactive protein and also other clinical conditions in rheumatoid arthritis Intern. Med. 50 2011 269 275
204. M. Bokarewa et al. Resistin, an adipokine with potent proinflammatory properties J. Immunol. 174 2005 5789 5795 (Pubitemid 40593223)
205. M.A. Gonzalez-Gay et al. Anti-TNF-alpha therapy modulates resistin in patients with rheumatoid arthritis Clin. Exp. Rheumatol. 26 2008 311 316 (Pubitemid 351659139)
206. J.T. Giles et al. Association of circulating adiponectin levels with progression of radiographic joint destruction in rheumatoid arthritis Ann. Rheum. Dis. 70 2009 1562 1568
207. P. Kontunen et al. Resistin is linked to inflammation, and leptin to metabolic syndrome, in women with inflammatory arthritis Scand. J. Rheumatol. 40 2011 256 262
208. A. Straburzynska-Lupa et al. Visfatin, resistin, hsCRP and insulin resistance in relation to abdominal obesity in women with rheumatoid arthritis Clin. Exp. Rheumatol. 28 2010 19 24
209. H. Forsblad d'Elia et al. Resistin in serum is associated with higher levels of IL-1Ra in post-menopausal women with rheumatoid arthritis Rheumatology 47 2008 1082 1087
210. E.A. Bostrom et al. Resistin and insulin/insulin-like growth factor signaling in rheumatoid arthritis Arthritis Rheum. 63 2011 2894 2904
211. N. Borregaard, and J.B. Cowland Neutrophil gelatinase-associated lipocalin, a siderophore-binding eukaryotic protein Biometals 19 2006 211 215 (Pubitemid 43794830)
212. S. Chakraborty et al. The multifaceted roles of neutrophil gelatinase associated lipocalin (NGAL) in inflammation and cancer Biochim. Biophys. Acta 1826 2012 129 169
213. S. Triebel et al. A 25 kDa alpha 2-microglobulin-related protein is a component of the 125 kDa form of human gelatinase FEBS Lett. 314 1992 386 388 (Pubitemid 23005695)
214. L. Kjeldsen et al. Identification of neutrophil gelatinase-associated lipocalin as a novel matrix protein of specific granules in human neutrophils Blood 83 1994 799 807 (Pubitemid 24043742)
215. L. Kjeldsen et al. Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse Biochim. Biophys. Acta 1482 2000 272 283
216. L. Kjeldsen et al. Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase J. Biol. Chem. 268 1993 10425 10432 (Pubitemid 23150227)
217. L.R. Devireddy et al. Induction of apoptosis by a secreted lipocalin that is transcriptionally regulated by IL-3 deprivation Science 293 2001 829 834 (Pubitemid 32743967)
218. S.T. Chu et al. The hydrophobic pocket of 24p3 protein from mouse uterine luminal fluid: fatty acid and retinol binding activity and predicted structural similarity to lipocalins J. Pept. Res. 52 1998 390 397
219. J.B. Cowland, and N. Borregaard Molecular characterization and pattern of tissue expression of the gene for neutrophil gelatinase-associated lipocalin from humans Genomics 45 1997 17 23 (Pubitemid 27449379)
220. J. Yang et al. An iron delivery pathway mediated by a lipocalin Mol. Cell 10 2002 1045 1056 (Pubitemid 35453824)
221. D.H. Goetz et al. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition Mol. Cell 10 2002 1033 1043 (Pubitemid 36001971)
222. D.R. Richardson 24p3 and its receptor: dawn of a new iron age? Cell 123 2005 1175 1177 (Pubitemid 41821772)
223. L.R. Devireddy et al. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake Cell 123 2005 1293 1305 (Pubitemid 41821786)
224. H.C. Owen et al. Dexamethasone-induced expression of the glucocorticoid response gene lipocalin 2 in chondrocytes Am. J. Physiol. Endocrinol. Metab. 294 2008 E1023 E1034
225. J. Conde et al. Expanding the adipokine network in cartilage: identification and regulation of novel factors in human and murine chondrocytes Ann. Rheum. Dis. 70 2011 551 559
226. K. Gupta et al. Neutrophil gelatinase-associated lipocalin is expressed in osteoarthritis and forms a complex with matrix metalloproteinase 9 Arthritis Rheum. 56 2007 3326 3335 (Pubitemid 47585427)
227. M. Katano et al. Implication of granulocyte-macrophage colony-stimulating factor induced neutrophil gelatinase-associated lipocalin in pathogenesis of rheumatoid arthritis revealed by proteome analysis Arthritis Res. Ther. 11 2009 R3
228. S. Bartsch, and H. Tschesche Cloning and expression of human neutrophil lipocalin cDNA derived from bone marrow and ovarian cancer cells FEBS Lett. 357 1995 255 259
229. V. Wittamer et al. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids J. Exp. Med. 198 2003 977 985 (Pubitemid 37248614)
230. I. Gantz et al. Molecular cloning of a novel receptor (CMKLR1) with homology to the chemotactic factor receptors Cytogenet. Cell. Genet. 74 1996 286 290 (Pubitemid 26402292)
231. V. Berg et al. Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin(21-157) Arthritis Res. Ther. 12 2010 R228
232. K. Bozaoglu et al. Chemerin is a novel adipokine associated with obesity and metabolic syndrome Endocrinology 148 2007 4687 4694 (Pubitemid 47481514)
233. S. Luangsay et al. Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model J. Immunol. 183 2009 6489 6499
234. S. Muruganandan et al. Role of chemerin/CMKLR1 signaling in adipogenesis and osteoblastogenesis of bone marrow stem cells J. Bone Miner. Res. 25 2010 222 234
235. K. Eisinger et al. Chemerin induces CCL2 and TLR4 in synovial fibroblasts of patients with rheumatoid arthritis and osteoarthritis Exp. Mol. Pathol. 92 2012 90 96
236. K. Huang et al. Association of chemerin levels in synovial fluid with the severity of knee osteoarthritis Biomarkers 17 2012 16 20
237. K. Kaneko et al. Chemerin activates fibroblast-like synoviocytes in patients with rheumatoid arthritis Arthritis Res. Ther. 13 2011 R158
238. K. Tatemoto et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor Biochem. Biophys. Res. Commun. 251 1998 471 476 (Pubitemid 28505047)
239. J. Boucher et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity Endocrinology 146 2005 1764 1771 (Pubitemid 40396885)
240. D. Daviaud et al. TNFalpha up-regulates apelin expression in human and mouse adipose tissue FASEB J. 20 2006 1528 1530
241. P.F. Hu et al. Apelin plays a catabolic role on articular cartilage: in vivo and in vitro studies Int. J. Mol. Med. 26 2010 357 363
242. K. Hida et al. Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity Proc. Natl. Acad. Sci. U. S. A. 102 2005 10610 10615 (Pubitemid 41061602)
243. N. Kamio et al. Vaspin attenuates RANKL-induced osteoclast formation in RAW264.7 cells Connect. Tissue Res. 54 2013 147 152
244. X. Zhu et al. Vaspin attenuates the apoptosis of human osteoblasts through ERK signaling pathway Amino Acids 44 2012 961 968
245. M. Ozgen et al. Serum adiponectin and vaspin levels in rheumatoid arthritis Arch. Med. Res. 41 2010 457 463
246. L. Senolt et al. Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis Ann. Rheum. Dis. 69 2010 1410 1411
247. R.T. White et al. Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue J. Biol. Chem. 267 1992 9210 9213
248. G. Fantuzzi Adipose tissue, adipokines, and inflammation J. Allergy Clin. Immunol. 115 2005 911 920 (Pubitemid 40616201)