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Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

ABSTRACT: A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allele showed no transcriptional response. Young adult volunteers (n = 187) were enrolled into a baseline study, and subjects with specific rs28357094 genotypes enrolled into an eccentric muscle challenge intervention [n = 3 TT; n = 3 GG/GT (dominant inheritance model)]. Female volunteers carrying the G allele showed significantly greater inflammation and increased muscle volume change as determined by magnetic resonance imaging T1- and T2-weighted images after eccentric challenge, as well as greater decrement in biceps muscle force. Our data suggest a model where the G allele enables enhanced activities of upstream enhancer elements due to loss of Sp1 binding at the polymorphic site. This results in significantly greater expression of the pro-inflammatory OPN cytokine during tissue remodeling in response to challenge in G allele carriers, promoting muscle hypertrophy in normal females, but increased damage in DMD patients.

SUBMITTER: Barfield WL

PROVIDER: S-EPMC4082368 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

Barfield Whitney L WL Uaesoontrachoon Kitipong K Wu Chung-Sheih CS Lin Stephen S Chen Yue Y Wang Paul C PC Kanaan Yasmine Y Bond Vernon V Hoffman Eric P EP

Human molecular genetics 20140313 15

A promoter polymorphism of the osteopontin (OPN) gene (rs28357094) has been associated with multiple inflammatory states, severity of Duchenne muscular dystrophy (DMD) and muscle size in healthy young adults. We sought to define the mechanism of action of the polymorphism, using allele-specific in vitro reporter assays in muscle cells, and a genotype-stratified intervention in healthy controls. In vitro reporter constructs showed the G allele to respond to estrogen treatment, whereas the T allel ...[more]

PMID: 24626632

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Project description:The current consensus in exercise physiology is that the repeated bout effect always appears after few eccentric exercise sessions. This is the first attempt to challenge this tenet, by exploiting specificity in muscle plasticity. More specifically, we examined whether the opposing adaptations in muscle induced after concentric and eccentric exercise can attenuate and/or remove the repeated bout effect. Seventeen young men were randomly assigned into one of the following groups: (1) the alternating eccentric-concentric exercise group; and (2) the eccentric-only exercise group. Both groups performed 8 weeks of resistance exercise using the knee extensors of both legs on an isokinetic dynamometer. The alternating eccentric-concentric exercise group performed an alternating exercise protocol, switching between eccentric-only and concentric-only exercise every 4 weeks, while the eccentric-only group performed eccentric exercise. Evaluation of muscle damage using physiological (isometric torque, delayed onset muscle soreness, and range of movement) and biochemical (creatine kinase) markers and inflammation (C-reactive protein) was performed at weeks 1, 5, and 10. Baseline isometric peak torque was also evaluated at week 14 after another cycle (4 weeks) of alternating or eccentric-only exercise training. In the alternating eccentric-concentric exercise group, the concentric exercise training performed prior to eccentric exercise reduced dramatically the repeated bout effect by reversing muscle back to its unaccustomed state. On the contrary, the eccentric-only exercise group exhibited a typical manifestation of the repeated bout effect. Interestingly, muscle strength was elevated similarly for both alternating and eccentric-only exercise groups after 13 weeks of training. The alternating eccentric-concentric exercise scheme, implemented in the present study, has for the first time successfully overcame the repeated bout effect. The similarity in muscle strength measurements following the two protocols is against the notion that inflammation plays an important role in exercise-induced adaptations in muscle.

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Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

Publications

Eccentric muscle challenge shows osteopontin polymorphism modulation of muscle damage.

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