Muscle Gene Expression Patterns in Human Rotator Cuff Pathology

The activity-dependent neuroprotective protein (ADNP), a double-edged sword, sex-dependently regulates multiple genes and was previously associated with the control of early muscle development and aging. Here we aimed to decipher the involvement of ADNP in versatile muscle gene expression patterns in correlation with motor function throughout life. Using quantitative RT-PCR we showed that Adnp+/− heterozygous deficiency in mice resulted in aberrant gastrocnemius (GC) muscle, tongue and bladder gene expression, which was corrected by the Adnp snippet, drug candidate, NAP (CP201). A significant sexual dichotomy was discovered, coupled to muscle and age-specific gene regulation. As such, Adnp was shown to regulate myosin light chain (Myl) in the gastrocnemius (GC) muscle, the language acquisition gene forkhead box protein P2 (Foxp2) in the tongue and the pituitary-adenylate cyclase activating polypeptide (PACAP) receptor PAC1 mRNA (Adcyap1r1) in the bladder, with PACAP linked to bladder function. A tight age regulation was observed, coupled to an extensive correlation to muscle function (gait analysis), placing ADNP as a muscle-regulating gene/protein.

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Lessons we can learn from gene expression patterns in rotator cuff tears and tendinopathies

Journal of Shoulder and Elbow Surgery ◽

10.1016/j.jse.2011.10.022 ◽

2012 ◽

Vol 21 (2) ◽

pp. 191-199 ◽

Cited By ~ 18

Author(s):

Salma Chaudhury ◽

Andrew J. Carr

Keyword(s):

Gene Expression ◽

Rotator Cuff ◽

Expression Patterns ◽

Rotator Cuff Tears ◽

Gene Expression Patterns

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Influence of age, sex, and strength training on human muscle gene expression determined by microarray

Physiological Genomics ◽

10.1152/physiolgenomics.00028.2002 ◽

2002 ◽

Vol 10 (3) ◽

pp. 181-190 ◽

Cited By ~ 82

Author(s):

Stephen M. Roth ◽

Robert E. Ferrell ◽

David G. Peters ◽

E. Jeffrey Metter ◽

Ben F. Hurley ◽

...

Keyword(s):

Gene Expression ◽

Strength Training ◽

Differential Expression ◽

Quantitative Pcr ◽

Expression Patterns ◽

Differentially Expressed ◽

Vastus Lateralis Muscle ◽

Men And Women ◽

Muscle Gene Expression ◽

Muscle Gene

The purpose of this study was to determine the influence of age, sex, and strength training (ST) on large-scale gene expression patterns in vastus lateralis muscle biopsies using high-density cDNA microarrays and quantitative PCR. Muscle samples from sedentary young (20–30 yr) and older (65–75 yr) men and women (5 per group) were obtained before and after a 9-wk unilateral heavy resistance ST program. RNA was hybridized to cDNA filter microarrays representing ∼4,000 known human genes and comparisons were made among arrays to determine differential gene expression as a result of age and sex differences, and/or response to ST. Sex had the strongest influence on muscle gene expression, with differential expression (>1.7-fold) observed for ∼200 genes between men and women (∼75% with higher expression in men). Age contributed to differential expression as well, as ∼50 genes were identified as differentially expressed (>1.7-fold) in relation to age, representing structural, metabolic, and regulatory gene classes. Sixty-nine genes were identified as being differentially expressed (>1.7-fold) in all groups in response to ST, and the majority of these were downregulated. Quantitative PCR was employed to validate expression levels for caldesmon, SWI/SNF (BAF60b), and four-and-a-half LIM domains 1. These significant differences suggest that in the analysis of skeletal muscle gene expression issues of sex, age, and habitual physical activity must be addressed, with sex being the most critical variable.

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