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Obesity, Osteoarthritis and Aging: The Biomechanical Links

  • Yao Fu
  • Timothy M. GriffinEmail author
Chapter
Part of the Studies in Mechanobiology, Tissue Engineering and Biomaterials book series (SMTEB, volume 16)

Abstract

Obesity increases osteoarthritis (OA) risk in both knee and hand joints, although the greatest impact is on the knee. The accelerated onset of OA that occurs with obesity has major health and financial consequences for individuals and society. Thus, it is critical to understand how obesity increases the risk of OA to develop effective strategies to prevent disease onset and/or slow disease progression. Obesity alters knee joint loading by increasing the knee adduction moment; however, it is difficult to predict how obesity affects the local cartilage mechanical environment because obesity alters joint loading frequency, magnitude, and duration both positively and negatively depending on the anatomical location and time-scale of analysis. In particular, obesity is associated with significant reductions in overall physical activity levels. Recent advances in the use of MRI to quantify in vivo diurnal strains provide a new approach for identifying the net effect of obesity on articular cartilage deformation. A growing number of clinical and animal studies indicate a role for systemic factors, such as high dietary fat and excess adiposity, in increasing OA risk. Adipose tissue secretes immunoregulatory molecules called adipokines, which are increasingly recognized for their ability to perturb joint tissue homeostasis. However, identifying a specific role for systemic inflammatory factors in knee OA pathogenesis is not well understood due to the challenge of isolating the biomechanical aspects of aging and obesity from the inflammatory changes. Identifying the role of adipokines in modifying OA risk is expected to require a better understanding of the connection between (1) systemic and local joint inflammation, and (2) the interaction of inflammatory and biomechanical signaling pathways. In this chapter, we review how changes in biomechanical stimulation associated with obesity and aging may increase OA risk by modifying cartilage susceptibility to inflammation and oxidative stress-mediated catabolic pathways.

Keywords

Mitochondrial Reactive Oxygen Species Joint Loading Mitochondrial Reactive Oxygen Species Production Knee Adduction Moment Joint Stress 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Felson, D.T., Lawrence, R.C., Dieppe, P.A., et al.: Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann. Intern. Med. 133, 635–646 (2000)Google Scholar
  2. 2.
    Loeser, R.F., Goldring, S.R., Scanzello, C.R., Goldring, M.B.: Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum. 64, 1697–1707 (2012)Google Scholar
  3. 3.
    Sandell, L.J.: Etiology of osteoarthritis: genetics and synovial joint development. Nat. Rev. Rheumatol. 8(2), 77–89 (2012)Google Scholar
  4. 4.
    Zhang, Y., Jordan, J.M.: Epidemiology of osteoarthritis. Clin. Geriatr. Med. 26(3), 355–369 (2010)Google Scholar
  5. 5.
    Felson, D.T., Zhang, Y., Hannan, M.T., et al.: Risk factors for incident radiographic knee osteoarthritis in the elderly: the Framingham study. Arthritis Rheum. 40, 728–733 (1997)Google Scholar
  6. 6.
    Muthuri, S.G., Hui, M., Doherty, M., Zhang, W.: What if we prevent obesity? Risk reduction in knee osteoarthritis estimated through a meta-analysis of observational studies. Arthritis Care Res. 63, 982–990 (2011)Google Scholar
  7. 7.
    Grotle, M., Hagen, K.B., Natvig, B., et al.: Obesity and osteoarthritis in knee, hip and/or hand: an epidemiological study in the general population with 10 years follow-up. BMC Musculoskelet Disord. 9, 132 (2008)Google Scholar
  8. 8.
    Yusuf, E., Nelissen, R.G., Ioan-Facsinay, A., et al.: Association between weight or body mass index and hand osteoarthritis: a systematic review. Ann. Rheum. Dis. 69, 761–765 (2010)Google Scholar
  9. 9.
    Oliveria, S.A., Felson, D.T., Cirillo, P.A., et al.: Body weight, body mass index, and incident symptomatic osteoarthritis of the hand, hip, and knee. Epidemiology 10(2), 161–166 (1999)Google Scholar
  10. 10.
    Losina, E., Weinstein, A.M., Reichmann, W.M., et al.: Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the US. Arthritis Care Res. 65, 703–711 (2013)Google Scholar
  11. 11.
    Losina, E., Daigle, M.E., Suter, L.G., et al.: Disease-modifying drugs for knee osteoarthritis: can they be cost-effective? Osteoarthritis Cartilage 21, 655–667 (2013)Google Scholar
  12. 12.
    Weinstein, A.M., Rome, B.N., Reichmann, W.M., et al.: Estimating the burden of total knee replacement in the United States. J. Bone Joint Surg. Am. 95, 385–392 (2013)Google Scholar
  13. 13.
    Kurtz, S.: Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J. Bone Joint Surg. Am. 89, 780–785 (2007)Google Scholar
  14. 14.
    Andriacchi, T.P.: Osteoarthritis: probing knee OA as a system responding to a stimulus. Nat. Rev. Rheumatol. 8, 371–372 (2012)Google Scholar
  15. 15.
    Felson, D.T.: Osteoarthritis as a disease of mechanics. Osteoarthritis Cartilage 21, 10–15 (2013)Google Scholar
  16. 16.
    Guilak, F.: Biomechanical factors in osteoarthritis. Best Pract Res Clin Rheumatol. 25, 815–823 (2011)Google Scholar
  17. 17.
    Messier, S.P.: Obesity and osteoarthritis: disease genesis and nonpharmacologic weight management. Med. Clin. North Am. 93, 145–159, xi–xii (2009)Google Scholar
  18. 18.
    Runhaar, J., Koes, B.W., Clockaerts, S., Bierma-Zeinstra, S.M.A.: A systematic review on changed biomechanics of lower extremities in obese individuals: a possible role in development of osteoarthritis. Obes. Rev. 12, 1071–1082 (2011)Google Scholar
  19. 19.
    DeVita, P., Hortobagyi, T.: Obesity is not associated with increased knee joint torque and power during level walking. J. Biomech. 36, 1355–1362 (2003)Google Scholar
  20. 20.
    Messier, S., DeVita, P., Cowan, R., et al.: Do older adults with knee osteoarthritis place greater loads on the knee during gait? A preliminary study. Arch. Phys. Med. Rehabil. 86, 703–709 (2005)Google Scholar
  21. 21.
    Browning, R.C., Kram, R.: Effects of obesity on the biomechanics of walking at different speeds. Med. Sci. Sports Exerc. 39, 1632–1641 (2007)Google Scholar
  22. 22.
    Miyazaki, T., Wada, M., Kawahara, H., et al.: Dynamic load at baseline can predict radiographic disease progression in medial compartment knee osteoarthritis. Ann. Rheum. Dis. 61, 617–622 (2002)Google Scholar
  23. 23.
    Andriacchi, T.P., Mündermann, A.: The role of ambulatory mechanics in the initiation and progression of knee osteoarthritis. Curr. Opin. Rheumatol. 18, 514–518 (2006)Google Scholar
  24. 24.
    Sharma, L., Song, J., Felson, D.T., et al.: The role of knee alignment in disease progression and functional decline in knee osteoarthritis. JAMA 286, 188–195 (2001)Google Scholar
  25. 25.
    Sharma, L., Chmiel, J.S., Almagor, O., et al.: The role of varus and valgus alignment in the initial development of knee cartilage damage by MRI: the MOST study. Ann. Rheum. Dis. 72, 235–240 (2012)Google Scholar
  26. 26.
    Hunter, D.J., Niu, J., Felson, D.T., et al.: Knee alignment does not predict incident osteoarthritis: the Framingham osteoarthritis study. Arthritis Rheum. 56, 1212–1218 (2007)Google Scholar
  27. 27.
    Sharma, L., Song, J., Dunlop, D., et al.: Varus and valgus alignment and incident and progressive knee osteoarthritis. Ann. Rheum. Dis. 69, 1940–1945 (2010)Google Scholar
  28. 28.
    Sharma, L., Lou, C., Cahue, S., Dunlop, D.D.: The mechanism of the effect of obesity in knee osteoarthritis: the mediating role of malalignment. Arthritis Rheum. 43, 568–575 (2000)Google Scholar
  29. 29.
    Brouwer, G.M., Tol, A.W.V., Bergink, A.P., et al.: Association between valgus and varus alignment and the development and progression of radiographic osteoarthritis of the knee. Arthritis Rheum. 56, 1204–1211 (2007)Google Scholar
  30. 30.
    Blazek, K., Asay, J.L., Hledik, J.E.: Adduction moment increases with age in healthy obese individuals. J. Orthop. Res. 31, 1414–1422 (2013)Google Scholar
  31. 31.
    Dutil, M., Handrigan, G.A., Corbeil, P., et al.: The impact of obesity on balance control in community-dwelling older women. Age (Dordr) 35, 883–890 (2013)Google Scholar
  32. 32.
    Hu, F.B., Li, T.Y., Colditz, G.A., et al.: Television watching and other sedentary behaviors in relation to risk of obesity and type 2 diabetes mellitus in women. JAMA 289, 1785–1791 (2003)Google Scholar
  33. 33.
    Hagströmer, M., Oja, P., Sjöström, M.: Physical activity and inactivity in an adult population assessed by accelerometry. Med. Sci. Sports Exerc. 39, 1502–1508 (2007)Google Scholar
  34. 34.
    Levine, J.A., Lanningham-Foster, L.M., McCrady, S.K., et al.: Interindividual variation in posture allocation: possible role in human obesity. Science 307, 584–586 (2005)Google Scholar
  35. 35.
    Lee, J., Song, J., Hootman, J.M., et al.: Obesity and other modifiable factors for physical inactivity measured by accelerometer in adults with knee osteoarthritis. Arthritis Care Res. 65, 53–61 (2013)Google Scholar
  36. 36.
    Griffin, T.M., Guilak, F.: The role of mechanical loading in the onset and progression of osteoarthritis. Exerc. Sport Sci. Rev. 33, 195–200 (2005)Google Scholar
  37. 37.
    Koo, S., Andriacchi, T.P.: A comparison of the influence of global functional loads vs. local contact anatomy on articular cartilage thickness at the knee. J. Biomech. 40, 2961–2966 (2007)Google Scholar
  38. 38.
    Blazek, K., Favre, J., Asay, J., et al.: Age and obesity alter the relationship between femoral articular cartilage thickness and ambulatory loads in individuals without osteoarthritis. J. Orthop. Res. 32, 394–402 (2014)Google Scholar
  39. 39.
    Eckstein, F.: In vivo cartilage deformation after different types of activity and its dependence on physical training status. Ann. Rheum. Dis. 64, 291–295 (2005)Google Scholar
  40. 40.
    Cotofana, S., Eckstein, F., Wirth, W., et al.: In vivo measures of cartilage deformation: patterns in healthy and osteoarthritic female knees using 3T MR imaging. Eur. Radiol. 21, 1127–1135 (2011)Google Scholar
  41. 41.
    Coleman, J.L., Widmyer, M.R., Leddy, H.A., et al.: Diurnal variations in articular cartilage thickness and strain in the human knee. J. Biomech. 46, 541–547 (2013)Google Scholar
  42. 42.
    Widmyer, M.R., Utturkar, G.M., Leddy, H.A., et al.: High body mass index is associated with increased diurnal strains in the articular cartilage of the knee. Arthritis Rheum. 65, 2615–2622 (2013)Google Scholar
  43. 43.
    Mosher, T.J., Walker, E.A., Petscavage-Thomas, J., Guermazi, A.: Osteoarthritis year 2013 in review: imaging. Osteoarthritis Cartilage 21, 1425–1435 (2013)Google Scholar
  44. 44.
    Ding, C., Stannus, O., Cicuttini, F., et al.: Body fat is associated with increased and lean mass with decreased knee cartilage loss in older adults: a prospective cohort study. Int. J. Obes. (2005). (2012). doi: 10.1038/ijo.2012.136
  45. 45.
    Aspden, R.M.: Obesity punches above its weight in osteoarthritis. Nat. Rev. Rheumatol. 7, 65–68 (2010)Google Scholar
  46. 46.
    Issa, R.I., Griffin, T.M.: Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation. Pathobiol. Aging Age Relat. Dis. 2, 17470 (2012)Google Scholar
  47. 47.
    Houard, X., Goldring, M.B., Berenbaum, F.: Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr. Rheumatol. Rep. 15, 375 (2013)Google Scholar
  48. 48.
    Presle, N., Pottie, P., Dumond, H., 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, 690–695 (2006)Google Scholar
  49. 49.
    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) 52, 1077–1083 (2013)Google Scholar
  50. 50.
    Lewis, J.S., Furman, B.D., Zeitler, E., et al.: Genetic and cellular evidence of decreased inflammation associated with reduced post-traumatic arthritis in MRL/MpJ mice. Arthritis Rheum. 65, 660–670 (2013)Google Scholar
  51. 51.
    Lee, J.H., Ort, T., Ma, K., 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, 613–620 (2009)Google Scholar
  52. 52.
    Mooney, R.A., Sampson, E.R., Lerea, J., et al.: High-fat diet accelerates progression of osteoarthritis after meniscal/ligamentous injury. Arthritis Res. Ther. 13, R198 (2011)Google Scholar
  53. 53.
    Huang, M.J., Wang, L., Jin, D.D., et al.: Enhancement of the synthesis of n-3 PUFAs in fat-1 transgenic mice inhibits mTORC1 signalling and delays surgically induced osteoarthritis in comparison with wild-type mice. Ann. Rheum. Dis. (2013). doi: 10.1136/annrheumdis-2013-203231. [Epub ahead of print]
  54. 54.
    Brunner, A.M., Henn, C.M., Drewniak, E.I., et al.: High dietary fat and the development of osteoarthritis in a rabbit model. Osteoarthritis Cartilage 20, 584–592 (2012)Google Scholar
  55. 55.
    Triantaphyllidou, I.-E., Kalyvioti, E., Karavia, E., et al.: Perturbations in the HDL metabolic pathway predispose to the development of osteoarthritis in mice following long-term exposure to western-type diet. Osteoarthritis Cartilage 21, 322–330 (2013)Google Scholar
  56. 56.
    Shi, H., Kokoeva, M.V., Inouye, K., et al.: TLR4 links innate immunity and fatty acid–induced insulin resistance. J Clin Invest. 116, 3015–3025 (2006)Google Scholar
  57. 57.
    Liu-Bryan, R., Terkeltaub, R.: Chondrocyte innate immune MyD88-dependent signaling drives pro-catabolic effects of the endogenous TLR2/TLR4 ligands LMW-HA and HMGB1. Arthritis Rheum. 62, 2004–2012 (2010)Google Scholar
  58. 58.
    Schelbergen, R.F.P., Blom, A.B., van den Bosch, M.H.J., et al.: Alarmins S100A8 and S100A9 elicit a catabolic effect in human osteoarthritic chondrocytes that is dependent on toll-like receptor 4. Arthritis Rheum. 64, 1477–1487 (2012)Google Scholar
  59. 59.
    Bonner, W.M., Jonsson, H., Malanos, C., Bryant, M.: Changes in the lipids of human articular cartilage with age. Arthritis Rheum. 18, 461–473 (1975)Google Scholar
  60. 60.
    Lippiello, L., Walsh, T., Fienhold, M.: The association of lipid abnormalities with tissue pathology in human osteoarthritic articular cartilage. Metabolism 40, 571–576 (1991)Google Scholar
  61. 61.
    Gierman, L.M., Wopereis, S., van El, B., et al.: Metabolic profiling reveals differences in concentrations of oxylipins and fatty acids secreted by the infrapatellar fat pad of end-stage osteoarthritis and normal donors. Arthritis Rheum. 65, 2606–2614 (2013)Google Scholar
  62. 62.
    Griffin, T.M., Huebner, J.L., Kraus, V.B., Guilak, F.: Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis. Arthritis Rheum. 60, 2935–2944 (2009)Google Scholar
  63. 63.
    Gierman, L.M., van der Ham, F., Koudijs, A., et al.: Metabolic stress-induced inflammation plays a major role in the development of osteoarthritis in mice. Arthritis Rheum. 64, 1172–1181 (2012)Google Scholar
  64. 64.
    Kerkhof, H.J., Doherty, M., Arden, N.K., et al.: Large-scale meta-analysis of interleukin-1 beta and interleukin-1 receptor antagonist polymorphisms on risk of radiographic hip and knee osteoarthritis and severity of knee osteoarthritis. Osteoarthritis Cartilage 19, 265–271 (2011)Google Scholar
  65. 65.
    Kraus, V.B., Birmingham, J., Stabler, T.V., et al.: Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254). Osteoarthritis Cartilage 20, 271–278 (2012)Google Scholar
  66. 66.
    Goekoop, R.J., Kloppenburg, M., Kroon, H.M., et al.: Low innate production of interleukin-1beta and interleukin-6 is associated with the absence of osteoarthritis in old age. Osteoarthritis Cartilage 18, 942–947 (2010)Google Scholar
  67. 67.
    Zhang, Y.: Prevalence of symptomatic hand osteoarthritis and its impact on functional status among the elderly: the Framingham study. Am. J. Epidemiol. 156, 1021–1027 (2002)Google Scholar
  68. 68.
    Dahaghin, S., Bierma-Zeinstra, S.M., Koes, B.W., et al.: Do metabolic factors add to the effect of overweight on hand osteoarthritis? The rotterdam study. Ann. Rheum. Dis. 66, 916–920 (2007)Google Scholar
  69. 69.
    Jonsson, H., Helgadottir, G.P., Aspelund, T., et al.: Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study. Ann. Rheum. Dis. 68, 1696–1700 (2009)Google Scholar
  70. 70.
    Haugen, I.K., Ramachandran, V.S., Misra, D., et al.: Hand osteoarthritis in relation to mortality and incidence of cardiovascular disease: data from the Framingham Heart Study. Ann Rheum Dis. (2013). doi: 10.1136/annrheumdis-2013-203789. [Epub ahead of print]
  71. 71.
    Visser, A.W., Ioan-Facsinay, A., de Mutsert, R., et al.: Adiposity and hand osteoarthritis: the Netherlands epidemiology of obesity study. Arthritis Res. Ther. 16, R19 (2014)Google Scholar
  72. 72.
    Massengale, M., Reichmann, W.M., 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 14, R132 (2012)Google Scholar
  73. 73.
    Massengale, M., Lu, B., Pan, J.J., et al.: Adipokine hormones and hand osteoarthritis: radiographic severity and pain. PLoS ONE 7, e47860 (2012)Google Scholar
  74. 74.
    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. 70, 1282–1284 (2011)Google Scholar
  75. 75.
    Griffin, T.M., Huebner, J.L., Kraus, V.B., et al.: Induction of osteoarthritis and metabolic inflammation by a very high-fat diet in mice: effects of short-term exercise. Arthritis Rheum. 64, 443–453 (2012)Google Scholar
  76. 76.
    Lago, R., Gomez, R., Otero, M., et al.: A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes. Osteoarthritis Cartilage 16, 1101–1109 (2008)Google Scholar
  77. 77.
    Kang, E.H., Lee, Y.J., Kim, T.K., et al.: Adiponectin is a potential catabolic mediator in osteoarthritis cartilage. Arthritis Res. Ther. 12, R231 (2010)Google Scholar
  78. 78.
    Koskinen, A., Juslin, S., Nieminen, R., 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, R184 (2011)Google Scholar
  79. 79.
    Chen, T.-H., Chen, L., Hsieh, M.-S., et al.: Evidence for a protective role for adiponectin in osteoarthritis. Biochim. Biophys. Acta 1762, 711–718 (2006)Google Scholar
  80. 80.
    Bijsterbosch, J., Meulenbelt, I., Watt, I., et al.: Clustering of hand osteoarthritis progression and its relationship to progression of osteoarthritis at the knee. Ann. Rheum. Dis. 73, 567–572 (2013)Google Scholar
  81. 81.
    Friedman, J.M., Halaas, J.L.: Leptin and the regulation of body weight in mammals. Nature 395, 763–770 (1998)Google Scholar
  82. 82.
    Karvonen-Gutierrez, C.A., Harlow, S.D., 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. (2013). doi: 10.1136/annrheumdis-2012-202685 [Epub ahead of print]
  83. 83.
    Griffin, T.M., Fermor, B., Huebner, J.L., et al.: Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice. Arthritis Res. Ther. 12, R130 (2010)Google Scholar
  84. 84.
    Otero, M., Gomez-Reino, J.J., Gualillo, O.: 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, 404–409 (2003)Google Scholar
  85. 85.
    Hui, W., Litherland, G.J., Elias, M.S., et al.: Leptin produced by joint white adipose tissue induces cartilage degradation via upregulation and activation of matrix metalloproteinases. Ann. Rheum. Dis. 71, 455–462 (2012)Google Scholar
  86. 86.
    Otero, M., Lago, R., Lago, F., 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, R581–R591 (2005)Google Scholar
  87. 87.
    Pallu, S., Francin, P.-J., Guillaume, C., et al.: Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis. Arthritis Res. Ther. 12, R112 (2010)Google Scholar
  88. 88.
    Vuolteenaho, K., Koskinen, A., Moilanen, T., Moilanen, E.: 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, 1912–1913 (2012)Google Scholar
  89. 89.
    Iliopoulos, D., Malizos, K.N., Tsezou, A.: Epigenetic regulation of leptin affects MMP-13 expression in osteoarthritic chondrocytes: possible molecular target for osteoarthritis therapeutic intervention. Ann. Rheum. Dis. 66, 1616–1621 (2007)Google Scholar
  90. 90.
    Simopoulou, T., Malizos, K.N., Iliopoulos, D., 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, 872–883 (2007)Google Scholar
  91. 91.
    Gleeson, M., Bishop, N.C., Stensel, D.J., et al.: The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat. Rev. Immunol. 11, 607–615 (2011)Google Scholar
  92. 92.
    Lavie, C.J., Church, T.S., Milani, R.V., Earnest, C.P.: Impact of physical activity, cardiorespiratory fitness, and exercise training on markers of inflammation. J. Cardiopulm. Rehabil. Prev. 31, 137–145 (2011)Google Scholar
  93. 93.
    Helmark, I.C., Mikkelsen, U.R., Børglum, J., et al.: Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis: a randomized controlled trial. Arthritis Res. Ther. 12, R126 (2010)Google Scholar
  94. 94.
    Agarwal, S., Deschner, J., Long, P., et al.: Role of NF-kappaB transcription factors in antiinflammatory and proinflammatory actions of mechanical signals. Arthritis Rheum. 50, 3541–3548 (2004)Google Scholar
  95. 95.
    Nam, J., Aguda, B.D., Rath, B., Agarwal, S.: Biomechanical thresholds regulate inflammation through the NF-kappaB pathway: experiments and modeling. PLoS ONE 4, e5262 (2009)Google Scholar
  96. 96.
    Torzilli, P.A., Bhargava, M., Park, S., Chen, C.T.C.: Mechanical load inhibits IL-1 induced matrix degradation in articular cartilage. Osteoarthritis Cartilage 18, 97–105 (2010)Google Scholar
  97. 97.
    Chowdhury, T.T., Arghandawi, S., Brand, J., et al.: Dynamic compression counteracts IL-1beta induced inducible nitric oxide synthase and cyclo-oxygenase-2 expression in chondrocyte/agarose constructs. Arthritis Res. Ther. 10, R35 (2008)Google Scholar
  98. 98.
    Akanji, O.O., Sakthithasan, P., Salter, D.M., Chowdhury, T.T.: Dynamic compression alters NFkappaB activation and IkappaB-alpha expression in IL-1beta-stimulated chondrocyte/agarose constructs. Inflamm. Res. 59, 41–52 (2010)Google Scholar
  99. 99.
    Nam, J., Perera, P., Liu, J., et al.: Transcriptome-wide gene regulation by gentle treadmill walking during the progression of monoiodoacetate-induced arthritis. Arthritis Rheum. 63, 1613–1625 (2011)Google Scholar
  100. 100.
    Torzilli, P.A., Bhargava, M., Chen, C.T.: Mechanical loading of articular cartilage reduces il-1-induced enzyme expression. Cartilage 2, 364–373 (2011)Google Scholar
  101. 101.
    Li, Y., Frank, E.H., Wang, Y., et al.: Moderate dynamic compression inhibits pro-catabolic response of cartilage to mechanical injury, tumor necrosis factor-α and interleukin-6, but accentuates degradation above a strain threshold. Osteoarthritis Cartilage 21, 1933–1941 (2013)Google Scholar
  102. 102.
    Henrotin, Y., Kurz, B., Aigner, T.: Oxygen and reactive oxygen species in cartilage degradation: friends or foes?1. Osteoarthritis Cartilage 13, 643–654 (2005)Google Scholar
  103. 103.
    Blanco, F.J., Rego, I., Ruiz-Romero, C.: The role of mitochondria in osteoarthritis. Nat. Rev. Rheumatol. 7, 161–169 (2011)Google Scholar
  104. 104.
    Lotz, M., Loeser, R.F.: Effects of aging on articular cartilage homeostasis. Bone 51, 241–248 (2012)Google Scholar
  105. 105.
    Nordberg, J., Arnér, E.S.: Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic. Biol. Med. 31, 1287–1312 (2001)Google Scholar
  106. 106.
    Henrotin, Y., Blanco, F., Aigner, T., Kurz, B.: The significance of oxidative stress in articular cartilage ageing and degradation. Curr. Rheumatol. Rev. 3, 261–274 (2007)Google Scholar
  107. 107.
    Stone, J.R., Yang, S.: Hydrogen peroxide: a signaling messenger. Antioxid. Redox Signal. 8, 243–270 (2006)Google Scholar
  108. 108.
    Go, Y.-M., Jones, D.P.: The redox proteome. J. Biol. Chem. 288, 26512–26520 (2013)Google Scholar
  109. 109.
    Abramson, S.B.: Osteoarthritis and nitric oxide. Osteoarthritis Cartilage 16(Suppl 2), S15–S20 (2008)Google Scholar
  110. 110.
    Martin, J.A., Martini, A., Molinari, A., et al.: Mitochondrial electron transport and glycolysis are coupled in articular cartilage. Osteoarthritis Cartilage 20, 323–329 (2012)Google Scholar
  111. 111.
    Gibson, J.S., Milner, P.I., White, R., et al.: Oxygen and reactive oxygen species in articular cartilage: modulators of ionic homeostasis. Pflugers. Arch. Eur. J. Physiol. 455, 563–573 (2007)Google Scholar
  112. 112.
    Wolff, K.J., Ramakrishnan, P.S., Brouillette, M.J., et al.: Mechanical stress and ATP synthesis are coupled by mitochondrial oxidants in articular cartilage. J. Orthop. Res. 31, 191–196 (2013)Google Scholar
  113. 113.
    Goodwin, W., McCabe, D., Sauter, E., et al.: Rotenone prevents impact-induced chondrocyte death. J. Orthop. Res. 28, 1057–1063 (2010)Google Scholar
  114. 114.
    Fermor, B., Weinberg, J.B., Pisetsky, D.S., et al.: The effects of static and intermittent compression on nitric oxide production in articular cartilage explants. J. Orthop. Res. 19, 729–737 (2001)Google Scholar
  115. 115.
    Maneiro, E., López-Armada, M.J., de Andres, M.C., et al.: Effect of nitric oxide on mitochondrial respiratory activity of human articular chondrocytes. Ann. Rheum. Dis. 64, 388–395 (2005)Google Scholar
  116. 116.
    Del Carlo, M., Loeser, R.F.: Nitric oxide-mediated chondrocyte cell death requires the generation of additional reactive oxygen species. Arthritis Rheum. 46, 394–403 (2002)Google Scholar
  117. 117.
    Anderson, D.D., Chubinskaya, S., Guilak, F., et al.: Post-traumatic osteoarthritis: improved understanding and opportunities for early intervention. J. Orthop. Res. 29, 802–809 (2011)Google Scholar
  118. 118.
    Buckwalter, J.A., Anderson, D.D., Brown, T.D., et al.: The roles of mechanical stresses in the pathogenesis of osteoarthritis: implications for treatment of joint injuries. Cartilage. (2013). doi: 10.1177/1947603513495889
  119. 119.
    Gavriilidis, C., Miwa, S., von Zglinicki, T., et al.: Mitochondrial dysfunction in osteoarthritis is associated with down-regulation of superoxide dismutase 2. Arthritis Rheum. 65, 378–387 (2013)Google Scholar
  120. 120.
    López-Armada, M., Carames, B., Martin, M., et al.: Mitochondrial activity is modulated by TNFα and IL-1β in normal human chondrocyte cells. Osteoarthritis Cartilage 14, 1011–1022 (2006)Google Scholar
  121. 121.
    Shikhman, A.R., Brinson, D.C., Valbracht, J., Lotz, M.K.: Cytokine regulation of facilitated glucose transport in human articular chondrocytes. J. Immunol. 167, 7001–7008 (2001)Google Scholar
  122. 122.
    Jones, D.P.: Redefining oxidative stress. Antioxid. Redox Signal. 8, 1865–1879 (2006)Google Scholar
  123. 123.
    Del Carlo, M., Loeser, R.F.: Increased oxidative stress with aging reduces chondrocyte survival: Correlation with intracellular glutathione levels. Arthritis Rheum. 48, 3419–3430 (2003)Google Scholar
  124. 124.
    Aigner, T., Fundel, K., Saas, J., et al.: Large-scale gene expression profiling reveals major pathogenetic pathways of cartilage degeneration in osteoarthritis. Arthritis Rheum. 54, 3533–3544 (2006)Google Scholar
  125. 125.
    Regan, E., Flannelly, J., Bowler, R., et al.: Extracellular superoxide dismutase and oxidant damage in osteoarthritis. Arthritis Rheum. 52, 3479–3491 (2005)Google Scholar
  126. 126.
    Ruiz-Romero, C., López-Armada, M.J., Blanco, F.J.: Mitochondrial proteomic characterization of human normal articular chondrocytes. Osteoarthritis Cartilage 14, 507–518 (2006). doi: 10.1016/j.joca.2005.12.004 Google Scholar
  127. 127.
    Ruiz-Romero, C., Calamia, V., Mateos, J., et al.: Mitochondrial dysregulation of osteoarthritic human articular chondrocytes analyzed by proteomics: a decrease in mitochondrial superoxide dismutase points to a redox imbalance. Mol. Cell. Proteomics 8, 172–189 (2009)Google Scholar
  128. 128.
    Scott, J.L., Gabrielides, C., Davidson, R.K., et al.: Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease. Ann. Rheum. Dis. 69, 1502–1510 (2010)Google Scholar
  129. 129.
    Baur, A., Henkel, J., Bloch, W., et al.: Effect of exercise on bone and articular cartilage in heterozygous manganese superoxide dismutase (SOD2) deficient mice. Free Rad Res. 45, 550–558 (2011)Google Scholar
  130. 130.
    Kurz, B., Lemke, A.K., Fay, J., et al.: Pathomechanisms of cartilage destruction by mechanical injury. Ann Anat. 187, 473–485 (2005)Google Scholar
  131. 131.
    Yamazaki, K., Fukuda, K., Matsukawa, M., et al.: Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: involvement of reactive oxygen species. Arthritis Rheum. 48, 3151–3158 (2003)Google Scholar
  132. 132.
    Sachdev, S., Davies, K.J.: Production, detection, and adaptive responses to free radicals in exercise. Free Radic. Biol. Med. 44, 215–223 (2008)Google Scholar
  133. 133.
    Matsuzaki, S., Szweda, P.A., Szweda, L.I., Humphries, K.M.: Regulated production of free radicals by the mitochondrial electron transport chain: cardiac ischemic preconditioning. Adv. Drug Deliv. Rev. 61, 1324–1331 (2009)Google Scholar
  134. 134.
    Kamata, H., Hirata, H.: Redox regulation of cellular signalling. Cell. Signal. 11, 1–14 (1999)Google Scholar
  135. 135.
    Ray, P.D., Huang, B.-W., Tsuji, Y.: Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell. Signal. 24, 981–990 (2012)Google Scholar
  136. 136.
    Mathy-Hartert, M., Hogge, L., Sanchez, C., et al.: Interleukin-1β and interleukin-6 disturb the antioxidant enzyme system in bovine chondrocytes: a possible explanation for oxidative stress generation. Osteoarthritis Cartilage 16, 756–763 (2008)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Free Radical Biology and Aging Research ProgramOklahoma Medical Research FoundationOklahoma CityUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA
  3. 3.Department of Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

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