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Impaired Myofibrillar Function in the Soleus Muscle of Mice With Collagen-Induced Arthritis
KTH, School of Engineering Sciences (SCI), Mechanics, Structural Mechanics.
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2009 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 11, 3280-3289 p.Article in journal (Refereed) Published
Abstract [en]

Objective. Progressive muscle weakness is a common feature in patients with rheumatoid arthritis (RA). However, little is known about whether the intrinsic contractile properties of muscle fibers are affected in RA. This study was undertaken to investigate muscle contractility and the myoplasmic free Ca2+ concentration ([Ca2+](i)) in the soleus, a major postural muscle, in mice with collagen-induced arthritis (CIA). Methods. Muscle contractility and [Ca2+](i) were assessed in whole muscle and intact single-fiber preparations, respectively. The underlying mechanisms of contractile dysfunction were assessed by investigating redox modifications using Western blotting and antibodies against nitric oxide synthase (NOS), superoxide dismutase (SOD), 3-nitrotyrosine (3-NT), carbonyl, malondialdehyde (MDA), and S-nitrosocysteine (SNO-Cys). Results. The tetanic force per cross-sectional area was markedly decreased in the soleus muscle of mice with CIA, and the change was not due to a decrease in the amplitude of [Ca2+](i) transients. The reduction in force production was accompanied by slowing of the twitch contraction and relaxation and a decrease in the maximum shortening velocity. Immunoblot analyses showed a marked increase in neuronal NOS expression but not in inducible or endothelial NOS expression, which, together with the observed decrease in SOD2 expression, favors peroxynitrite formation. These changes were accompanied by increased 3-NT, carbonyl, and MDA adducts content in myofibrillar proteins from the muscles of mice with CIA. Moreover, there was a significant increase in SNO-Cys content in myosin heavy-chain and troponin I myofibrillar proteins from the soleus muscle of mice with CIA. Conclusion. These findings show impaired contractile function in the soleus muscle of mice with CIA and suggest that this abnormality is due to peroxynitrite-induced modifications in myofibrillar proteins.

Place, publisher, year, edition, pages
2009. Vol. 60, no 11, 3280-3289 p.
National Category
Rheumatology and Autoimmunity
URN: urn:nbn:se:kth:diva-33118DOI: 10.1002/art.24907ISI: 000271781400017PubMedID: 19877058ScopusID: 2-s2.0-70350555329OAI: diva2:413481
Swedish Research Council
QC 20110428Available from: 2011-04-28 Created: 2011-04-28 Last updated: 2012-05-25Bibliographically approved
In thesis
1. Modelling of muscular force induced by non-isometric contraction
Open this publication in new window or tab >>Modelling of muscular force induced by non-isometric contraction
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The main objective of the study was to investigate and simulate skeletal muscleforce production during and after isometric contractions, active muscle lengtheningand active muscle shortening. The motivation behind this work was to improve thedominant model of muscle force generation based on the theories of Hill from 1938. Effects of residual force enhancement and force depression were observed after concentric and eccentric contractions, and also during stretch-shortening cycles. It wasshown that this force modification is not related to lengthening/shortening velocity, butinstead the steady-state force after non-isometric contractions can be well describedby an initial isometric force to which a modification is added. The modification isevaluated from the mechanical work performed by and on the muscle during lengthvariations. The time constants calculated for isometric force redevelopment appearedto be in certain relations with those for initial isometric force development, an observation which extended our basis for muscle modelling.

A macroscopic muscular model consisting of a contractile element, and paralleland series elastic elements was supplemented with a history component and adoptedfor mouse soleus muscle experiments. The parameters from the experiment analysis, particularly the force modification after non-isometric contractions and the timeconstants, were reproduced by the simulations. In a step towards a general implementation, the history modification was introduced in the muscluloskeletal model ofOpenSim software, which was then used for simulations of full body movements.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2012. x, 48 p.
Trita-MEK, ISSN 0348-467X ; 2012:03
Skeletal muscle, Muscular force, Concentric contractions, Eccentric con- tractions, History effect, Force modification, Muscle model, Musculoskeletal model
National Category
Applied Mechanics
urn:nbn:se:kth:diva-95418 (URN)978-91-7501-399-8 (ISBN)
Public defence
2012-05-31, E2, Lindstedtsvägen 3, KTH, Stockholm, 10:00 (English)
QC 20120525Available from: 2012-05-25 Created: 2012-05-24 Last updated: 2012-05-25Bibliographically approved

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