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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
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)
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)
Sandell, L.J.: Etiology of osteoarthritis: genetics and synovial joint development. Nat. Rev. Rheumatol. 8(2), 77–89 (2012)
Zhang, Y., Jordan, J.M.: Epidemiology of osteoarthritis. Clin. Geriatr. Med. 26(3), 355–369 (2010)
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)
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)
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 10Â years follow-up. BMC Musculoskelet Disord. 9, 132 (2008)
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)
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)
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)
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)
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)
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)
Andriacchi, T.P.: Osteoarthritis: probing knee OA as a system responding to a stimulus. Nat. Rev. Rheumatol. 8, 371–372 (2012)
Felson, D.T.: Osteoarthritis as a disease of mechanics. Osteoarthritis Cartilage 21, 10–15 (2013)
Guilak, F.: Biomechanical factors in osteoarthritis. Best Pract Res Clin Rheumatol. 25, 815–823 (2011)
Messier, S.P.: Obesity and osteoarthritis: disease genesis and nonpharmacologic weight management. Med. Clin. North Am. 93, 145–159, xi–xii (2009)
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)
DeVita, P., Hortobagyi, T.: Obesity is not associated with increased knee joint torque and power during level walking. J. Biomech. 36, 1355–1362 (2003)
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)
Browning, R.C., Kram, R.: Effects of obesity on the biomechanics of walking at different speeds. Med. Sci. Sports Exerc. 39, 1632–1641 (2007)
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)
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)
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)
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)
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)
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)
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)
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)
Blazek, K., Asay, J.L., Hledik, J.E.: Adduction moment increases with age in healthy obese individuals. J. Orthop. Res. 31, 1414–1422 (2013)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Mosher, T.J., Walker, E.A., Petscavage-Thomas, J., Guermazi, A.: Osteoarthritis year 2013 in review: imaging. Osteoarthritis Cartilage 21, 1425–1435 (2013)
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
Aspden, R.M.: Obesity punches above its weight in osteoarthritis. Nat. Rev. Rheumatol. 7, 65–68 (2010)
Issa, R.I., Griffin, T.M.: Pathobiology of obesity and osteoarthritis: integrating biomechanics and inflammation. Pathobiol. Aging Age Relat. Dis. 2, 17470 (2012)
Houard, X., Goldring, M.B., Berenbaum, F.: Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr. Rheumatol. Rep. 15, 375 (2013)
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)
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)
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)
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)
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)
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]
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)
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)
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)
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)
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)
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)
Lippiello, L., Walsh, T., Fienhold, M.: The association of lipid abnormalities with tissue pathology in human osteoarthritic articular cartilage. Metabolism 40, 571–576 (1991)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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]
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)
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)
Massengale, M., Lu, B., Pan, J.J., et al.: Adipokine hormones and hand osteoarthritis: radiographic severity and pain. PLoS ONE 7, e47860 (2012)
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)
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)
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)
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)
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)
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)
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)
Friedman, J.M., Halaas, J.L.: Leptin and the regulation of body weight in mammals. Nature 395, 763–770 (1998)
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]
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
Torzilli, P.A., Bhargava, M., Chen, C.T.: Mechanical loading of articular cartilage reduces il-1-induced enzyme expression. Cartilage 2, 364–373 (2011)
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)
Henrotin, Y., Kurz, B., Aigner, T.: Oxygen and reactive oxygen species in cartilage degradation: friends or foes?1. Osteoarthritis Cartilage 13, 643–654 (2005)
Blanco, F.J., Rego, I., Ruiz-Romero, C.: The role of mitochondria in osteoarthritis. Nat. Rev. Rheumatol. 7, 161–169 (2011)
Lotz, M., Loeser, R.F.: Effects of aging on articular cartilage homeostasis. Bone 51, 241–248 (2012)
Nordberg, J., Arnér, E.S.: Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic. Biol. Med. 31, 1287–1312 (2001)
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)
Stone, J.R., Yang, S.: Hydrogen peroxide: a signaling messenger. Antioxid. Redox Signal. 8, 243–270 (2006)
Go, Y.-M., Jones, D.P.: The redox proteome. J. Biol. Chem. 288, 26512–26520 (2013)
Abramson, S.B.: Osteoarthritis and nitric oxide. Osteoarthritis Cartilage 16(Suppl 2), S15–S20 (2008)
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)
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)
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)
Goodwin, W., McCabe, D., Sauter, E., et al.: Rotenone prevents impact-induced chondrocyte death. J. Orthop. Res. 28, 1057–1063 (2010)
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)
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)
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)
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)
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
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)
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)
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)
Jones, D.P.: Redefining oxidative stress. Antioxid. Redox Signal. 8, 1865–1879 (2006)
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)
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)
Regan, E., Flannelly, J., Bowler, R., et al.: Extracellular superoxide dismutase and oxidant damage in osteoarthritis. Arthritis Rheum. 52, 3479–3491 (2005)
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
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)
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)
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)
Kurz, B., Lemke, A.K., Fay, J., et al.: Pathomechanisms of cartilage destruction by mechanical injury. Ann Anat. 187, 473–485 (2005)
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)
Sachdev, S., Davies, K.J.: Production, detection, and adaptive responses to free radicals in exercise. Free Radic. Biol. Med. 44, 215–223 (2008)
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)
Kamata, H., Hirata, H.: Redox regulation of cellular signalling. Cell. Signal. 11, 1–14 (1999)
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)
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)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Fu, Y., Griffin, T.M. (2014). Obesity, Osteoarthritis and Aging: The Biomechanical Links. In: Gefen, A., Benayahu, D. (eds) The Mechanobiology of Obesity and Related Diseases. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 16. Springer, Cham. https://doi.org/10.1007/8415_2014_178
Download citation
DOI: https://doi.org/10.1007/8415_2014_178
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-09335-2
Online ISBN: 978-3-319-09336-9
eBook Packages: EngineeringEngineering (R0)