The Role of Sirtuins in Cartilage Homeostasis and Osteoarthritis

  • Mona Dvir-GinzbergEmail author
  • Ali Mobasheri
  • Ashok Kumar
Osteoarthritis (MB Goldring, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Osteoarthritis


The past decade has witnessed many advances in the understanding of sirtuin biology and related regulatory circuits supporting the capacity of these proteins to serve as energy-sensing molecules that contribute to healthspan in various tissues, including articular cartilage. Hence, there has been a significant increase in new investigations that aim to elucidate the mechanisms of sirtuin function and their roles in cartilage biology, skeletal development, and pathologies such as osteoarthritis (OA), rheumatoid arthritis (RA), and intervertebral disc degeneration (IVD). The majority of the work carried out to date has focused on SIRT1, although SIRT6 has more recently become a focus of some investigations. In vivo work with transgenic mice has shown that Sirt1 and Sirt6 are essential for maintaining cartilage homeostasis and that the use of sirtuin-activating molecules such as resveratrol may have beneficial effects on cartilage anabolism. Current thinking is that SIRT1 exerts positive effects on cartilage by encouraging chondrocyte survival, especially under stress conditions, which may provide a mechanism supporting the use of sirtuin small-molecule activators (STACS) for future therapeutic interventions in OA and other degenerative pathologies of joints, especially those that involve articular cartilage.


Sirtuin SIRT1 Cartilage Osteoarthritis (OA) Intervertebral disc (IVD) Degeneration Rheumatoid arthritis 



The authors acknowledge their funding support from the European Commission Framework 7 programme (EU FP7; HEALTH.2012.2.4.5-2, project number 305815, Novel Diagnostics and Biomarkers for Early Identification of Chronic Inflammatory Joint Diseases); The Israel Science Foundation (grant no. 121/12); USA-Israel Binational Science Foundation (BSF) (grant no. 2013145); Arthritis Research UK (grant no. 20786); and the Rosetrees Trust (grant no. A770). AK is a post-doctoral scholar supported by the Israeli Planning and Budgeting Committee (PBC) fellowship program.

Compliance with Ethical Standards

Conflicts of Interest

MDG, AM, and AK declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This review article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Mobasheri A, Matta C, Zákány R, Musumeci G. Chondrosenescence: definition, hallmarks and potential role in the pathogenesis of osteoarthritis. Maturitas. 2015;80(3):237–44.CrossRefPubMedGoogle Scholar
  2. 2.
    Iannone F, Lapadula G. The pathophysiology of osteoarthritis. Aging Clin Exp Res. 2003;15(5):364–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Hunter DJ, Schofield D, Callander E. The individual and socioeconomic impact of osteoarthritis. Nat Rev Rheumatol. 2014;10(7):437–41.PubMedGoogle Scholar
  4. 4.
    Malfait AM. Osteoarthritis year in review 2015: biology. Osteoarthritis Cartilage. 2016;24(1):21–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Bay-Jensen AC, Reker D, Kjelgaard-Petersen CF, Mobasheri A, Karsdal MA, Ladel C, et al. Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria. Osteoarthritis Cartilage. 2016;24(1):9–20.CrossRefPubMedGoogle Scholar
  6. 6.
    Peytremann-Bridevaux I, Faeh D, Santos-Eggimann B. Prevalence of overweight and obesity in rural and urban settings of 10 European countries. Prev Med. 2007;44(5):442–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Dvir-Ginzberg M, Gagarina V, Lee EJ, Hall DJ. Regulation of cartilage-specific gene expression in human chondrocytes by SirT1 and nicotinamide phosphoribosyltransferase. J Biol Chem. 2008;52:36300–10.CrossRefGoogle Scholar
  8. 8.
    Haigis MC, Sinclair DA. Mammalian sirtuins: biological insights and disease relevance. Annu Rev Pathol. 2010;5:253–95.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Sinclair DA, Guarente L. Extra chromosomal rDNA circles—a cause of aging in yeast. Cell. 1997;91(7):1033–42.CrossRefPubMedGoogle Scholar
  10. 10.
    Bordone L, Cohen D, Robinson A, Motta MC, van Veen E, Czopik A, et al. Guarente L.SIRT1 transgenic mice show phenotypes resembling calorie restriction. Aging Cell. 2007;6(6):759–67.CrossRefPubMedGoogle Scholar
  11. 11.
    Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, et al. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature. 2007;450(7170):712–6.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127(6):1109–22.CrossRefPubMedGoogle Scholar
  13. 13.
    McBurney MW, Clark-Knowles KV, Caron AZ, Gray DA. SIRT1 is a highly networked protein that mediates the adaptation to chronic physiological stress. Genes Cancer. 2013;4(3-4):125–34.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y. Nucleocytoplasmic shuttling of the NAD + -dependent histone deacetylase SIRT1. J Biol Chem. 2007;282(9):6823–32.CrossRefPubMedGoogle Scholar
  15. 15.
    Austin S, St-Pierre J. PGC1α and mitochondrial metabolism-emerging concepts and relevance in ageing and neurodegenerative disorders, J. Cell Sci. 2012;125(Pt 21):4963–71.Google Scholar
  16. 16.
    Morris BJ. Seven sirtuins for seven deadly diseases of aging, Free Radic. Biol. Med. 2013;56:133–71.Google Scholar
  17. 17.
    Southwood CM, Peppi M, Dryden S, Tainsky Ma, Gow A. Microtubule deacetylases, SirT2 and HDAC6, in the nervous system, Neurochem. Res. 2007;32:187–95.Google Scholar
  18. 18.
    Anderson KA, Green MF, Huynh FK, Wagner GR, Hirschey MD. SnapShot : mammalian sirtuins, Cell. 2014;159:956–956.Google Scholar
  19. 19.
    Brachmann CB, Sherman JM, Devine SE, Cameron EE, Pillus L, Boeke JD. The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability, Genes Dev. 1995;9:2888–902.Google Scholar
  20. 20.
    North BJ, Marshall BL, Borra MT, Denu JM, Verdin E, Francisco S. The human Sir2 ortholog, SIRT2, is an NAD-dependent tubulin deacetylase, Mol. Cell. 2003;11:437–44.Google Scholar
  21. 21.
    Scher MB, Vaquero A, Reinberg D. SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the mitochondria upon cellular stress, Genes Dev. 2007;21:920–8.Google Scholar
  22. 22.
    Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC, Murphy AJ, et al. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell. 2006;126(5):941–54.CrossRefPubMedGoogle Scholar
  23. 23.
    Nakagawa T, Lomb DJ, Haigis MC, Guarente L. SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell. 2009;137(3):560–70.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, et al. The sirtuin SIRT6 regulates lifespan in male mice. Nature. 2012;483(7388):218–21.CrossRefPubMedGoogle Scholar
  25. 25.
    Grob A, Roussel P, Wright JE, McStay B, Hernandez-Verdun D, Sirri V. Involvement of SIRT7 in resumption of rDNA transcription at the exit from mitosis. J Cell Sci. 2009;122(Pt 4):489–98.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.••
    Gabay O, Oppenhiemer H, Meir H, Zaal K, Sanchez C, Dvir-Ginzberg M. Increased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice. Ann Rheum Dis. 2012;71(4):613–6. First study to show SIRT1 relevance to OA in-vivo transgenic mice.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Gabay O, Zaal KJ, Sanchez C, Dvir-Ginzberg M, Gagarina V, Song Y, et al. Sirt1-deficient mice exhibit an altered cartilage phenotype. Joint Bone Spine. 2013;80(6):613–20.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Gabay O, Sanchez C, Dvir-Ginzberg M, Gagarina V, Zaal KJ, Song Y, et al. Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model. Arthritis Rheum. 2013;65(1):159–66.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.••
    Matsuzaki T, Matsushita T, Takayama K, Matsumoto T, Nishida K, Kuroda R, 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):1397–404. First study to show SIRT1 importance to DMM-induced OA in-vivo transgenic mice.Google Scholar
  30. 30.•
    Li W, Cai L, Zhang Y, Cui L, Shen G. Intra-articular resveratrol injection prevents osteoarthritis progression in a mouse model by activating SIRT1 and thereby silencing HIF-2α. J Orthop Res. 2015;33(7):1061–70. An in vivo investigation displaying protecting effects of resveratrol on articular cartilage degeneration.CrossRefPubMedGoogle Scholar
  31. 31.
    Lim HD, Kim YS, Ko SH, Yoon IJ, Cho SG, Chun YH, 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):225–37.CrossRefPubMedGoogle Scholar
  32. 32.
    Kim HJ, Braun HJ, Dragoo JL. The effect of resveratrol on normal and osteoarthritic chondrocyte metabolism. Bone Joint Res. 2014;3(3):51–9.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.•
    Xia X, Guo J, Lu F, Jiang J. SIRT1 plays a protective role in intervertebral disc degeneration in a puncture-induced rodent model. Spine (Phila Pa 1976). 2015;40(9):E515–24. First study to show the protective attributes of SIRT1 in IVD degeneration.CrossRefGoogle Scholar
  34. 34.
    Oppenheimer H, Kumar A, Meir H, Schwartz I, Zini A, Haze A, et al. Dvir-Ginzberg M Set7/9 impacts COL2A1 expression through binding and repression of SirT1 histone deacetylation. J Bone Miner Res. 2014;29(2):348–60.CrossRefPubMedGoogle Scholar
  35. 35.
    Fujita N, Matsushita T, Ishida K, Kubo S, Matsumoto T, Takayama 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):511–5.CrossRefPubMedGoogle Scholar
  36. 36.
    Hong EH, Yun HS, Kim J, Um HD, Lee KH, Kang CM, et al. 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. 2011;286(32):28619–31.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Matsushita T, Sasaki H, Takayama K, Ishida K, Matsumoto T, Kubo S, et al. The overexpression of SIRT1 inhibited osteoarthritic gene expression changes induced by interleukin-1β in human chondrocytes. J Orthop Res. 2013;31(4):531–7.CrossRefPubMedGoogle Scholar
  38. 38.
    Bar Oz M, Kumar A, Elayyan J, Reich E, Binyamin M, Kandel L, et al. Acetylation reduces SOX9 nuclear entry and ACAN gene transactivation in human chondrocytes. Aging Cell. 2016. doi: 10.1111/acel.12456.PubMedPubMedCentralGoogle Scholar
  39. 39.••
    Takayama K, Ishida K, Matsushita T, Fujita N, Hayashi S, Sasaki K, et al. SIRT1 regulation of apoptosis of human chondrocytes. Arthritis Rheum. 2009;60(9):2731–40. This paper elegantly shows the survival effect exerted by SIRT1 in chondrocytes, through its effect on mitochondrial proteins.CrossRefPubMedGoogle Scholar
  40. 40.
    Gagarina V, Gabay O, Dvir-Ginzberg M, Lee EJ, Brady JK, Quon MJ, 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 Rheum. 2010;62(5):1383–92.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.•
    Wang D, Hu Z, Hao J, He B, Gan Q, Zhong X, et al. SIRT1 inhibits apoptosis of degenerative human disc nucleuspulposus cells through activation of Akt pathway. Age (Dordr). 2013;35(5):1741–53. This work with nucleus pulposus (NP) cells supports that SIRT1 activates AKT pathway to prevent apoptosis.Google Scholar
  42. 42.••
    Jiang W, Zhang X, Hao J, Shen J, Fang J, Dong W, et al. SIRT1 protects against apoptosis by promoting autophagy in degenerative human disc nucleus pulposus cells. Sci Rep. 2014;4:7456. This report displays compelling data to support that human disc degeneration is repressed by the pro-survival attributes of SIRT1 via autophagy regulation.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Miyazaki S, Kakutani K, Yurube T, Maeno K, Takada T, Zhang Z, et al. Recombinant human SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human intervertebral disc nucleus pulposus cells. Arthritis Res Ther. 2015;17:253.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.••
    Lei M, Wang J, Xiao D, Fan M, Wang D, Xiong J, et al. Resveratrol inhibits interleukin 1β-mediated inducible nitric oxide synthase expression in articular chondrocytes by activating SIRT1 and thereby suppressing nuclear factor-κB activity. Eur J Pharmacol. 2012;674:73–9. This report shows the inhibitory impact of SIRT1 on RelA during pro-inflammatory stimuli.CrossRefPubMedGoogle Scholar
  45. 45.
    Hong EH, Lee SJ, Kim JS, Lee KH, Um HD, Kim JH, et al. Ionizing radiation induces cellular senescence of articular chondrocytes via negative regulation of SIRT1 by p38 kinase. J Biol Chem. 2010;285(2):1283–95.CrossRefPubMedGoogle Scholar
  46. 46.
    Brandl A, Hartmann A, Bechmann V, Graf B, Nerlich M, Angele P. Oxidative stress induces senescence in chondrocytes. J Orthop Res. 2011;29(7):1114–20.CrossRefPubMedGoogle Scholar
  47. 47.••
    Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009;458(7241):1056–60. This breakthrough study shows the impact of ATP and AMPK on SIRT1 activity via NAD metabolism, indicating that SIRT1 activity is also susceptible to energy expenditure.Google Scholar
  48. 48.••
    Wang Y, Zhao X, Lotz M, Terkeltaub R, Liu-Bryan R. Mitochondrial biogenesis is impaired in osteoarthritis chondrocytes but reversible via peroxisome proliferator-activated receptor γ coactivator 1α. Arthritis Rheumatol. 2015;67(8):2141–53. 48 and 49 are elegant reports highlighting the convergence between AMPK and SIRT1 in regulating chondrocyte energy status in OA pathogenesis.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Liu-Bryan R. Inflammation and intracellular metabolism: new targets in OA. Osteoarthritis Cartilage. 2015;23(11):1835–42.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Yang S, Ryu JH, Oh H, Jeon J, Kwak JS, Kim JH, et al. NAMPT (visfatin), a direct target of hypoxia-inducible factor-2α, is an essential catabolic regulator of osteoarthritis. Ann Rheum Dis. 2015;74(3):595–602.CrossRefPubMedGoogle Scholar
  51. 51.
    Oh H, Kwak JS, Yang S, Gong MK, Kim JH, Rhee J, et al. Reciprocal regulation by hypoxia-inducible factor-2α and the NAMPT-NAD(+)-SIRT axis in articular chondrocytes is involved in osteoarthritis. Osteoarthritis Cartilage. 2015;23(12):2288–96.CrossRefPubMedGoogle Scholar
  52. 52.•
    Yammani RR, Loeser RF. Extracellular nicotinamidephosphoribosyltransferase (NAMPT/visfatin) inhibits insulin-like growth factor-1 signaling and proteoglycan synthesis in human articular chondrocytes. Arthritis Res Ther. 2012;14(1):R23. First study to examine the endocrine effect of eNAMPT/visfatin in OA.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Laiguillon MC, Houard X, Bougault C, Gosset M, Nourissat G, Sautet A, et al. Expression and function of visfatin (Nampt), an adipokine-enzyme involved in inflammatory pathways of osteoarthritis. Arthritis Res Ther. 2014;16(1):R38.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Pecchi E. Induction of nerve growth factor expression and release by mechanical and inflammatory stimuli in chondrocytes: possible involvement in osteoarthritis pain. Arthritis Res Ther. 2014;16(1):R16.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Présumey J, Courties G, Louis-Plence P, Escriou V, Scherman D, Pers YM, et al. Nicotinamide phosphoribosyltransferase/visfatin expression by inflammatory monocytes mediates arthritis pathogenesis. Ann Rheum Dis. 2013;72(10):1717–24.CrossRefPubMedGoogle Scholar
  56. 56.•
    Dvir-Ginzberg M, Gagarina V, Lee EJ, Booth R, Gabay O, Hall DJ. Tumor necrosis factor α-mediated cleavage and inactivation of SirT1 in human osteoarthritic chondrocytes. Arthritis Rheum. 2011;63(8):2363–73. This report highlights that pro-inflammatory stimuli, causes SIRT1 truncation and inactivation in OA chondrocytes.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Gardner PJ, Yazid S, Chu CJ, Copland DA, Adamson P, Dick AD, et al. TNFα regulates SIRT1 cleavage during ocular autoimmune disease. Am J Pathol. 2015;185(5):1324–33.CrossRefPubMedGoogle Scholar
  58. 58.
    Chen J, Xavier S, Moskowitz-Kassai E, Chen R, Lu CY, Sanduski K, et al. Cathepsin cleavage of sirtuin 1 in endothelial progenitor cells mediates stress-induced premature senescence. Am J Pathol. 2012;180(3):973–83.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Ben-Aderet L, Merquiol E, Fahham D, Kumar A, Reich E, Ben-Nun Y, et al. Detecting cathepsin activity in human osteoarthritis via activity-based probes. Arthritis Res Ther. 2015;17:69.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.•
    Niederer F, Ospelt C, Brentano F, Hottiger MO, Gay RE, Gay S, et al. SIRT1 overexpression in the rheumatoid arthritis synovium contributes to proinflammatory cytokine production and apoptosis resistance. Ann Rheum Dis. 2011;70(10):1866–73. This is the first report showing how SIRT1 impact synovitis in rheumatoid arthritis.CrossRefPubMedGoogle Scholar
  61. 61.
    Kok SH, Lin LD, Hou KL, Hong CY, Chang CC, Hsiao M, et al. Simvastatin inhibits cysteine-rich protein 61 expression in rheumatoid arthritis synovial fibroblasts through the regulation of sirtuin-1/FoxO3a signaling. Arthritis Rheum. 2013;65(3):639–49.CrossRefPubMedGoogle Scholar
  62. 62.••
    Burnett C, Valentini S, Cabreiro F, Goss M, Somogyvári M, Piper MD, et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature. 2011;477(7365):482–5. This study shows that the effect of lifespan extension exerted by Sir2 may be influenced by adverse genetic background and thereby may not robustly present a significant extension in lifespan.Google Scholar
  63. 63.••
    Wu Y, Chen L, Wang Y, Li W, Lin Y, Yu D, et al. Overexpression of Sirtuin 6 suppresses cellular senescence and NF-Κb mediated inflammatory responses in osteoarthritis development. Sci Rep. 2015;5:17602. An important report showing that Sirt6 is a key regulator in OA pathogenesis.CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.•
    Nagai K, Matsushita T, Matsuzaki T, Takayama K, Matsumoto T, Kuroda R, et al. Depletion of SIRT6 causes cellular senescence, DNA damage, and telomere dysfunction in human chondrocytes. Osteoarthritis Cartilage. 2015;23(8):1412–20. An important report showing that Sirt6 protects from DNA damage in OA pathogenesis.CrossRefPubMedGoogle Scholar
  65. 65.••
    Piao J, Tsuji K, Ochi H, Iwata M, Koga D, Okawa A, et al. Sirt6 regulates postnatal growth plate differentiation and proliferation via Ihh signaling. Sci Rep. 2013;3:3022. An important report showing that Sirt6 regulates Ihh activity in cartilage growth plate.CrossRefPubMedGoogle Scholar
  66. 66.
    Lin J, Sun B, Jiang C, Hong H, Zheng Y. Sirt2 suppresses inflammatory responses in collagen-induced arthritis. Biochem Biophys Res Commun. 2013;441(4):897–903.CrossRefPubMedGoogle Scholar
  67. 67.•
    Lee HS, Ka SO, Lee SM, Lee SI, Park JW, Park BH. Overexpression of sirtuin 6 suppresses inflammatory responses and bone destruction in mice with collagen-induced arthritis. Arthritis Rheum. 2013;65(7):1776–85. In this report, Sirt6 is shown to reduce inflammation in a murine RA model.CrossRefPubMedGoogle Scholar
  68. 68.
    Engler A, Niederer F, Klein K, Gay RE, Kyburz D, Camici GG, et al. SIRT6 regulates the cigarette smoke-induced signaling in rheumatoid arthritis synovial fibroblasts. J Mol Med (Berl). 2014;92(7):757–67.CrossRefGoogle Scholar
  69. 69.••
    Fu Y, Kinter M, Hudson J, Humphries KM, Lane RS, White JR, et al. Aging promotes SIRT3-dependent cartilage SOD2 acetylation and osteoarthritis. Arthritis Rheumatol. 2016. doi: 10.1002/art.39618. [Epub ahead of print]. First paper to show that Sirt3 plays an essential role in OA via regulating mitochondrial activity.Google Scholar
  70. 70.
    Dieppe PA, Cushaghan D, Jasani MK, et al. A two year placebo controlled trial of non-steroidal anti-inflammatory therapy in osteoarthritis of the knee joint. Br J Rheumatol. 1993;32:595–600.CrossRefPubMedGoogle Scholar
  71. 71.
    Williams HJ, Ward JR, Egger MJ, et al. Comparison of naproxen and acetaminophen in a two year study of treatment of osteoarthritis of the knee. Arthritis Rheum. 1993;36:1196–206.CrossRefPubMedGoogle Scholar
  72. 72.
    Mobasheri A. Osteoarthritis year 2012 in review: biomarkers. Osteoarthritis Cartilage. 2012;20(12):1451–64.CrossRefPubMedGoogle Scholar
  73. 73.
    Rousseau JC, Delmas PD. Nat Clin Pract Rheumatol. 2007;3(6):346–56. Biological markers in osteoarthritis.Google Scholar
  74. 74.
    Jotanovic Z, Mihelic R, Sestan B, Dembic Z. Emerging pathways and promising agents with possible disease modifying effect in osteoarthritis treatment. Curr Drug Targets. 2014;15:635–661.Google Scholar
  75. 75.•
    Buhrmann C, Busch F, Shayan P, Shakibaei M. Sirtuin-1 (SIRT1) is required for promoting chondrogenic differentiation of mesenchymal stem cells. J Biol Chem. 2014;289(32):22048–62. Important paper presenting data to show that SIRT1 is essential for chondrogenesis of mesenchymal progenitors.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Edwards JR, Perrien DS, Fleming N, Nyman JS, Ono K, Connelly L, et al. Silent information regulator (Sir)T1 inhibits NF-κB signaling to maintain normal skeletal remodeling. J Bone Miner Res. 2013;28(4):960–9.CrossRefPubMedGoogle Scholar
  77. 77.
    Cohen-Kfir E, Artsi H, Levin A, Abramowitz E, Bajayo A, Gurt I, et al. Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin, a bone formation inhibitor. Endocrinology. 2011;152(12):4514–24.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Mona Dvir-Ginzberg
    • 1
    Email author
  • Ali Mobasheri
    • 2
    • 3
  • Ashok Kumar
    • 1
  1. 1.Institute of Dental Sciences, Faculty of Dental MedicineHebrew University of JerusalemJerusalemIsrael
  2. 2.Department of Veterinary Preclinical Sciences, School of Veterinary Medicine, Faculty of Health and Medical SciencesUniversity of SurreyGuildfordUK
  3. 3.Arthritis Research UK Centre for Sport, Exercise and Osteoarthritis, Queen’s Medical CentreNottinghamUK

Personalised recommendations