Temporal development of muscle atrophy in murine model of arthritis is related to disease severity
Tóm tắt
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unknown etiology, affecting mainly the joint but also other tissues. RA patients usually present weakness and muscle atrophy, nonarticular manifestations of the disease. Although causing great impact, the understanding of muscle atrophy, its development, and the mechanisms involved is still very limited. The objective of this study is to evaluate the development of muscle atrophy in skeletal muscle of a murine model of arthritis. The experimental murine model of collagen-induced arthritis (CIA) was used. DBA/1J mice were randomly divided into three groups: control (CO, n = 25), sham arthritis (SA, n = 25), and arthritis (CIA, n = 28), analyzed in different time points: 25, 35, and 45 days after the induction of arthritis. The arthritis development was followed by clinical scores and hind paw edema three times a week. The spontaneous exploratory locomotion and weight were evaluated weekly. In all time points, serum was collected before the death of the animals for cytokine analysis, and myofiber cross-sectional areas (CSA) of gastrocnemius (GA) and tibialis anterior (TA) skeletal muscles were evaluated. The clinical parameters of arthritis progressively increased in CIA in all experimental times, demonstrating the greatest difference from other groups at 45 days after induction (clinical score: CO, 00 ± 00; SA, 1.00 ± 0.14; CIA, 3.28 ± 0.41 p > 0.05). The CIA animals had lower weights during all the experimentation periods with a difference of 6 % from CO at 45 days (p > 0.05). CIA animals also demonstrated progressive decrease in distance walked, with a reduction of 54 % in 35 and 74 % at 45 days. Cytokine analysis identified significant increase in IL-6 serum levels in CIA than CO and SA in all experimental times. CSA of the myofiber of GA and TA was decreased 26 and 31 % (p > 0.05) in CIA in 45 days after the induction of disease, respectively. There was significant and inverse correlation between the disease clinical score and myofiber CSA in 45 days (GA: r = −0.71; p = 0.021). Our results point to a progressive development of muscle wasting, with premature onset arthritis. These observations are relevant to understand the development of muscle loss, as well as for the design of future studies trying to understand the mechanisms involved in muscle wasting. As far as we are concerned, this is the first study to evaluate the relation between disease score and muscle atrophy in a model of arthritis.
Tài liệu tham khảo
Glass D, Roubenoff R. Recent advances in the biology and therapy of muscle wasting. Ann N Y Acad Sci. 2010;1211:25–36.
Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358:903–11.
da Rochal OM et al. Sarcopenia da caquexia reumatoide:conceituação, mecanismos, consequências clínicas e tratamentos possíveis. Rev Bras Reumatol. 2009;49:288–301.
Evans WJ. Skeletal muscle loss: cachexia, sarcopenia, and inactivity. Am J Clin Nutr. 2010;91:1123S–7.
Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull. 2010;95:139–59.
Cruz-Jentoft AJ et al. Sarcopenia: European consensus on definition and diagnosis. Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010;39:412–23.
Cederholm TE et al. Toward a definition of sarcopenia. Clin Geriatr Med. 2011;27:341–53.
Tracey KJ et al. Metabolic effects of cachectin tumor-necrosis-factor are modified by site of production—cachectin tumor necrosis factor-secreting tumor in skeletal-muscle induces chronic cachexia, while implantation in brain induces predominately acute anorexia. J Clin Invest. 1990;86:2014–24.
Matschke V et al. Skeletal muscle properties in rheumatoid arthritis patients. Med Sci Sports Exerc. 2010;42:2149–55.
Rall LC et al. The effect of progressive resistance training in rheumatoid arthritis. Increased strength without changes in energy balance or body composition. Arthritis Rheum. 1996;39:415–26.
Granado M et al. Tumour necrosis factor blockade did not prevent the increase of muscular muscle RING finger-1 and muscle atrophy F-box in arthritic rats. J Endocrinol. 2006;191:319–26.
Ozawa J et al. Morphological changes in hind limb muscles elicited by adjuvant-induced arthritis of the rat knee. Scand J Med Sci Sports. 2010;20:e72–9.
Hartog A, Hulsman J, Garssen J. Locomotion and muscle mass measures in a murine model of collagen-induced arthritis. BMC Musculoskeletal Disord. 2009;10:59.
VDONT, Teixeira LIF, Viacava PR, Cerski MR, Xavier RM. Pathological and molecular changes in skeletal muscle of collagen induced arthritis. London: The European League Against Rheumatism; 2011
Brand DD, Latham KA, Rosloniec EF. Collagen-induced arthritis. Nat Protoc. 2007;2:1269–75.
Oliveira PG et al. Protective effect of RC-3095, an antagonist of the gastrin-releasing peptide receptor, in experimental arthritis. Arthritis Rheum. 2011;63:2956–65.
Brietzke E et al. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord. 2009;116:214–7.
Roubenoff R. Inflammatory and hormonal mediators of cachexia. J Nutr. 1997;127:1014S–6.
Okiura T et al. Bone density of the femur and fiber cross-sectional area and oxidative enzyme activity of the tilbialis anterior muscle in type II collagen-induced arthritic mice. J Physiol Sci. 2008;58:221–7.
Granado M et al. Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats. Am J Physiol Endocrinol Metab. 2005;288:E486–92.
Granado M et al. Experimental arthritis inhibits the insulin-like growth factor-I axis and induces muscle wasting through cyclooxygenase-2 activation. Am J Physiol Endocrinol Metab. 2007;292:E1656–65.
Castillero E et al. Fenofibrate, a PPAR{alpha} agonist, decreases atrogenes and myostatin expression and improves arthritis-induced skeletal muscle atrophy. Am J Physiol Endocrinol Metab. 2011;300:E790–9.
Balasubramaniam A et al. Ghrelin inhibits skeletal muscle protein breakdown in rats with thermal injury through normalizing elevated expression of E3 ubiquitin ligases MuRF1 and MAFbx. Am J Physiol Regul Integr Comp Physiol. 2009;296:R893–901.
Castillero E et al. Eicosapentaenoic acid attenuates arthritis-induced muscle wasting acting on atrogin-1 and on myogenic regulatory factors. Am J Physiol Regul Integr Comp Physiol. 2009;297:R1322–31.
Acharyya S et al. Cancer cachexia is regulated by selective targeting of skeletal muscle gene products. J Clin Invest. 2004;114:370–8.
Llovera M et al. Role of TNF receptor 1 in protein turnover during cancer cachexia using gene knockout mice. Mol Cell Endocrinol. 1998;142:183–9.
Setoguchi C et al. Combined effects of bucillamine and etanercept on a rat type II collagen-induced arthritis model. Mod Rheumatol. 2010;20:381–8.
Lon HK et al. Pharmacokinetic-pharmacodynamic disease progression model for effect of etanercept in Lewis rats with collagen-induced arthritis. Pharm Res. 2011;28:1622–30.
Braun TP et al. Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. J Exp Med. 2011;208:2449–63.
Roubenoff R et al. Adjuvant arthritis as a model of inflammatory cachexia. Arthritis Rheum. 1997;40:534–9.
Teixeira VD, Filippin LI, Xavier RM. Mechanisms of muscle wasting in sarcopenia. Rev Bras Reumatol. 2012;52:252–9.