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The current progress in understanding the molecular functions and mechanisms of visfatin in osteoarthritis

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Abstract

Osteoarthritis, (OA), also known as degenerative arthritis or degenerative joint disease, is the most common form of arthritis, affecting millions of people worldwide. It is a group of mechanical abnormalities involving degradation of the joints and occurs when the protective cartilage (articular cartilage) on the ends of bones such as the knees, hips and fingers abrades over time. It mainly affects the whole joint structure, including the articular cartilage, subchondral bone and synovial tissue. Extensive work has been done in the past decades to investigate the cellular mechanism of this disease. However, to date, it is still poorly understood, and there is no effective treatment. Recently, both in vitro and in vivo studies have confirmed adipokines play critical roles during OA development. Among these, leptin and adiponectin have been well investigated, whereas the effect of the novel adipokine, visfatin, on OA still needs to be revealed. Therefore, in this short review, we will focus on visfatin and summarize the current progress in the research on its role in OA development.

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References

  1. Felson DT, Anderson JJ, Naimark A, Walker AM, Meenan RF (1988) Obesity and knee osteoarthritis: the Framingham study. Ann Intern Med 109:18–24

    Article  CAS  PubMed  Google Scholar 

  2. Griffin TM, Fermor B, Huebner JL, Kraus VB, Rodriguiz RM, Wetsel WC, Cao L, Setton LA, Guilak F (2010) Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice. Arthritis Res Ther 12:R130

    Article  PubMed  PubMed Central  Google Scholar 

  3. Oliveria SA, Felson DT, Cirillo PA, Reed JI, Walker AM (1999) Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee. Epidemiology 10:161–166

    Article  CAS  PubMed  Google Scholar 

  4. Felson DT, Goggins J, Niu J, Zhang Y, Hunter DJ (2004) The effect of body weight on progression of knee osteoarthritis is dependent on alignment. Arthritis Rheum 50:3904–3909

    Article  PubMed  Google Scholar 

  5. Sharma L, Song J, Felson DT, Cahue S, Shamiyeh E, Dunlop DD (2001) The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA 286:188–195

    Article  CAS  PubMed  Google Scholar 

  6. Slemenda C, Heilman DK, Brandt KD, Katz BP, Mazzuca SA, Braunstein EM, Byrd D (1998) Reduced quadriceps strength relative to body weight: a risk factor for knee osteoarthritis in women? Arthritis Rheum 41:1951–1959

    Article  CAS  PubMed  Google Scholar 

  7. Vincent HK, Heywood K, Connelly J, Hurley RW (2012) Obesity and weight loss in the treatment and prevention of osteoarthritis. PM R 4:S59–S67

    Article  PubMed  PubMed Central  Google Scholar 

  8. Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, Pottie P (2003) Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum 48:3118–3129

    Article  CAS  PubMed  Google Scholar 

  9. Filkova M, Liskova M, Hulejova H, Haluzik M, Gatterova J, Pavelkova A, Pavelka K, Gay S, Muller-Ladner U, Senolt L (2009) Increased serum adiponectin levels in female patients with erosive compared with non-erosive osteoarthritis. Ann Rheum Dis 68:295–296

    Article  CAS  PubMed  Google Scholar 

  10. Francin PJ, Abot A, Guillaume C, Moulin D, Bianchi A, Gegout-Pottie P, Jouzeau JY, Mainard D, Presle N (2014) Association between adiponectin and cartilage degradation in human osteoarthritis. Osteoarthr Cartil 22:519–526

    Article  PubMed  Google Scholar 

  11. Griffin TM, Huebner JL, Kraus VB, Guilak F (2009) Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum 60:2935–2944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sandell LJ (2009) Obesity and osteoarthritis: is leptin the link? Arthritis Rheum 60:2858–2860

    Article  PubMed  Google Scholar 

  13. Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I (1994) Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol 14:1431–1437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Revollo JR, Grimm AA, Imai S (2004) The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J Biol Chem 279:50754–50763

    Article  CAS  PubMed  Google Scholar 

  15. Wang T, Zhang X, Bheda P, Revollo JR, Imai S, Wolberger C (2006) Structure of Nampt/PBEF/visfatin, a mammalian NAD + biosynthetic enzyme. Nat Struct Mol Biol 13:661–662

    Article  CAS  PubMed  Google Scholar 

  16. Khan JA, Tao X, Tong L (2006) Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents. Nat Struct Mol Biol 13:582–588

    Article  CAS  PubMed  Google Scholar 

  17. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426–430

    Article  CAS  PubMed  Google Scholar 

  18. Chang YH, Chang DM, Lin KC, Shin SJ, Lee YJ (2011) Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev 27:515–527

    Article  PubMed  Google Scholar 

  19. Hajianfar H, Bahonar A, Entezari MH, Askari G, Yazdani M (2012) Lipid profiles and serum visfatin concentrations in patients with type II diabetes in comparison with healthy controls. Int J Prev Med 3:326–331

    PubMed  PubMed Central  Google Scholar 

  20. Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, Milbrandt J, Kiess W, Imai S (2007) Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 6:363–375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Jia SH, Li Y, Parodo J, Kapus A, Fan L, Rotstein OD, Marshall JC (2004) Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 113:1318–1327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W (2015) Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol 11:535–546

    CAS  Google Scholar 

  23. Chen WP, Bao JP, Feng J, Hu PF, Shi ZL, Wu LD (2010) Increased serum concentrations of visfatin and its production by different joint tissues in patients with osteoarthritis. Clin Chem Lab Med 48:1141–1145

    CAS  PubMed  Google Scholar 

  24. Duan Y, Hao D, Li M, Wu Z, Li D, Yang X, Qiu G (2011) Increased synovial fluid visfatin is positively linked to cartilage degradation biomarkers in osteoarthritis. Rheumatol Int 32:985–990

    Article  PubMed  Google Scholar 

  25. Laiguillon MC, Houard X, Bougault C, Gosset M, Nourissat G, Sautet A, Jacques C, Berenbaum F, Sellam J (2014) Expression and function of visfatin (Nampt), an adipokine-enzyme involved in inflammatory pathways of osteoarthritis. Arthritis Res Ther 16:R38

    Article  PubMed  PubMed Central  Google Scholar 

  26. Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H (2007) Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 178:1748–1758

    Article  CAS  PubMed  Google Scholar 

  27. McNulty AL, Miller MR, O’Connor SK, Guilak F (2011) The effects of adipokines on cartilage and meniscus catabolism. Connect Tissue Res 52:523–533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chauffier K, Laiguillon MC, Bougault C, Gosset M, Priam S, Salvat C, Mladenovic Z, Nourissat G, Jacques C, Houard X, Berenbaum F, Sellam J (2012) Induction of the chemokine IL-8/Kc by the articular cartilage: possible influence on osteoarthritis. Joint Bone Spine 79:604–609

    Article  CAS  PubMed  Google Scholar 

  29. Klein-Wieringa IR, Kloppenburg M, Bastiaansen-Jenniskens YM, Yusuf E, Kwekkeboom JC, El-Bannoudi H, Nelissen RG, Zuurmond A, Stojanovic-Susulic V, Van Osch GJ, Toes RE, Ioan-Facsinay A (2011) The infrapatellar fat pad of patients with osteoarthritis has an inflammatory phenotype. Ann Rheum Dis 70:851–857

    Article  CAS  PubMed  Google Scholar 

  30. Chadjichristos C, Ghayor C, Kypriotou M, Martin G, Renard E, Ala-Kokko L, Suske G, de Crombrugghe B, Pujol JP, Galera P (2003) Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes. J Biol Chem 278:39762–39772

    Article  CAS  PubMed  Google Scholar 

  31. Hammacher A, Ward LD, Weinstock J, Treutlein H, Yasukawa K, Simpson RJ (1994) Structure-function analysis of human IL-6: identification of two distinct regions that are important for receptor binding. Protein Sci 3:2280–2293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Stove J, Huch K, Gunther KP, Scharf HP (2000) Interleukin-1beta induces different gene expression of stromelysin, aggrecan and tumor-necrosis-factor-stimulated gene 6 in human osteoarthritic chondrocytes in vitro. Pathobiology 68:144–149

    Article  CAS  PubMed  Google Scholar 

  33. Berenbaum F (2000) Proinflammatory cytokines, prostaglandins, and the chondrocyte: mechanisms of intracellular activation. Joint Bone Spine 67:561–564

    Article  CAS  PubMed  Google Scholar 

  34. Serhan CN, Levy B (2003) Success of prostaglandin E2 in structure-function is a challenge for structure-based therapeutics. Proc Natl Acad Sci USA 100:8609–8611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Smith WL (1989) The eicosanoids and their biochemical mechanisms of action. Biochem J 259:315–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Davies P, Bailey PJ, Goldenberg MM, Ford-Hutchinson AW (1984) The role of arachidonic acid oxygenation products in pain and inflammation. Annu Rev Immunol 2:335–357

    Article  CAS  PubMed  Google Scholar 

  37. Gosset M, Berenbaum F, Salvat C, Sautet A, Pigenet A, Tahiri K, Jacques C (2008) 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 58:1399–1409

    Article  CAS  PubMed  Google Scholar 

  38. Jacques C, Holzenberger M, Mladenovic Z, Salvat C, Pecchi E, Berenbaum F, Gosset M (2012) Proinflammatory actions of visfatin/nicotinamide phosphoribosyltransferase (Nampt) involve regulation of insulin signaling pathway and Nampt enzymatic activity. J Biol Chem 287:15100–15108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Smelter E, Hochberg MC (2013) New treatments for osteoarthritis. Curr Opin Rheumatol 25:310–316

    Article  CAS  PubMed  Google Scholar 

  40. Pecchi E, Priam S, Gosset M, Pigenet A, Sudre L, Laiguillon MC, Berenbaum F, Houard X (2014) Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain. Arthritis Res Ther 16:R16

    Article  PubMed  PubMed Central  Google Scholar 

  41. Yang S, Ryu JH, Oh H, Jeon J, Kwak JS, Kim JH, Kim HA, Chun CH, Chun JS (2013) NAMPT (visfatin), a direct target of hypoxia-inducible factor-2alpha, is an essential catabolic regulator of osteoarthritis. Ann Rheum Dis 74:595–602

    Article  PubMed  PubMed Central  Google Scholar 

  42. Oh H, Kwak JS, Yang S, Gong MK, Kim JH, Rhee J, Kim SK, Kim HE, Ryu JH, Chun JS (2015) Reciprocal regulation by hypoxia-inducible factor-2alpha and the NAMPT-NAD-SIRT axis in articular chondrocytes is involved in osteoarthritis. Osteoarthr Cartil 12:2288–2296

    Article  Google Scholar 

  43. Zhang T (1804) Kraus WL 2009 SIRT1-dependent regulation of chromatin and transcription: linking NAD(+) metabolism and signaling to the control of cellular functions. Biochim Biophys Acta 8:1666–1675

    Google Scholar 

  44. Liu-Bryan R, Terkeltaub R (2014) Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol 11:35–44

    Article  PubMed  PubMed Central  Google Scholar 

  45. Dvir-Ginzberg M, Steinmeyer J (2013) Towards elucidating the role of SirT1 in osteoarthritis. Front Biosci (Landmark Ed) 18:343–355

    Article  CAS  Google Scholar 

  46. Hong EH, Lee SJ, Kim JS, Lee KH, Um HD, Kim JH, Kim SJ, Kim JI, Hwang SG (2009) Ionizing radiation induces cellular senescence of articular chondrocytes via negative regulation of SIRT1 by p38 kinase. J Biol Chem 285:1283–1295

    Article  PubMed  PubMed Central  Google Scholar 

  47. Takayama K, Ishida K, Matsushita T, Fujita N, Hayashi S, Sasaki K, Tei K, Kubo S, Matsumoto T, Fujioka H, Kurosaka M, Kuroda R (2009) SIRT1 regulation of apoptosis of human chondrocytes. Arthritis Rheum 60:2731–2740

    Article  CAS  PubMed  Google Scholar 

  48. Dvir-Ginzberg M, Gagarina V, Lee EJ, Hall DJ (2008) Regulation of cartilage-specific gene expression in human chondrocytes by SirT1 and nicotinamide phosphoribosyltransferase. J Biol Chem 283:36300–36310

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hong EH, Yun HS, Kim J, Um HD, Lee KH, Kang CM, Lee SJ, Chun JS, Hwang SG (2011) Nicotinamide phosphoribosyltransferase is essential for interleukin-1beta-mediated dedifferentiation of articular chondrocytes via SIRT1 and extracellular signal-regulated kinase (ERK) complex signaling. J Biol Chem 286:28619–28631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Orton RJ, Sturm OE, Vyshemirsky V, Calder M, Gilbert DR, Kolch W (2005) Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem J 392:249–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yammani RR, Loeser RF (2012) Extracellular nicotinamide phosphoribosyltransferase (NAMPT/visfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes. Arthritis Res Ther 14:R23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopedics, The Second Xiangya Hospital of Central South University, 86 Renmin Middle Rd, Yuhua, Changsha, Hunan, China

    Lele Liao, Yiyue Chen & Wanchun Wang

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  1. Lele Liao
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  2. Yiyue Chen
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  3. Wanchun Wang
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Correspondence to Wanchun Wang.

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Liao, L., Chen, Y. & Wang, W. The current progress in understanding the molecular functions and mechanisms of visfatin in osteoarthritis. J Bone Miner Metab 34, 485–490 (2016). https://doi.org/10.1007/s00774-016-0743-1

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  • DOI: https://doi.org/10.1007/s00774-016-0743-1

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