title: Temporal development of muscle atrophy in murine model of arthritis is related to disease severity.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: Laboratório de Doenças Autoimunes e Infecciosas, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Bairro Rio Branco, CEP 90035-903, Porto Alegre, RS, Brazil, lidifilippin@gmail.com.
authors: Lidiane I
authors: LI
authors: Filippin
authors: Vivian N
authors: VN
authors: Teixeira
authors: Paula R
authors: PR
authors: Viacava
authors: Priscila S
authors: PS
authors: Lora
authors: Laura L
authors: LL
authors: Xavier
authors: Ricardo M
authors: RM
authors: Xavier
references: Arthritis Rheum. 2011 Oct;63(10):2956-65
references: 21953084
references: Ann N Y Acad Sci. 2010 Nov;1211:25-36
references: 21062293
references: Lancet. 2001 Sep 15;358(9285):903-11
references: 11567728
references: Br Med Bull. 2010;95:139-59
references: 20200012
references: Age Ageing. 2010 Jul;39(4):412-23
references: 20392703
references: Clin Geriatr Med. 2011 Aug;27(3):341-53
references: 21824551
references: Mod Rheumatol. 2010 Aug;20(4):381-8
references: 20379758
references: J Exp Med. 2011 Nov 21;208(12):2449-63
references: 22084407
references: J Endocrinol. 2006 Oct;191(1):319-26
references: 17065414
references: J Clin Invest. 1990 Dec;86(6):2014-24
references: 2254457
references: Arthritis Rheum. 1996 Mar;39(3):415-26
references: 8607890
references: Arthritis Rheum. 1997 Mar;40(3):534-9
references: 9082942
references: Am J Physiol Endocrinol Metab. 2005 Mar;288(3):E486-92
references: 15507538
references: J Clin Invest. 2004 Aug;114(3):370-8
references: 15286803
references: Pharm Res. 2011 Jul;28(7):1622-30
references: 21360252
references: Med Sci Sports Exerc. 2010 Dec;42(12):2149-55
references: 20404765
references: Am J Physiol Regul Integr Comp Physiol. 2009 Apr;296(4):R893-901
references: 19211729
references: J Affect Disord. 2009 Aug;116(3):214-7
references: 19251324
references: Am J Physiol Regul Integr Comp Physiol. 2009 Nov;297(5):R1322-31
references: 19741054
references: Am J Clin Nutr. 2010 Apr;91(4):1123S-1127S
references: 20164314
references: Rev Bras Reumatol. 2012 Mar-Apr;52(2):252-9
references: 22460414
references: Mol Cell Endocrinol. 1998 Jul 25;142(1-2):183-9
references: 9783914
references: J Nutr. 1997 May;127(5 Suppl):1014S-1016S
references: 9164287
references: J Physiol Sci. 2008 Aug;58(4):221-7
references: 18534044
references: Scand J Med Sci Sports. 2010 Feb;20(1):e72-9
references: 19555394
references: Am J Physiol Endocrinol Metab. 2011 May;300(5):E790-9
references: 21304067
references: Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1656-65
references: 17284570
references: BMC Musculoskelet Disord. 2009 Jun 03;10:59
references: 19493332
references: Nat Protoc. 2007;2(5):1269-75
references: 17546023