Influence of exercise intensity on training-induced tendon mechanical properties changes in older individuals.

This study compared the effects of low vs. high intensity training on tendon properties in an elderly population. Participants were pair-matched (gender, habitual physical activity, anthropometrics, and baseline knee extension strength) and then randomly assigned to low (LowR, i.e., ~40 % 1RM) or high (High R, i.e., ~80 % 1RM) intensity resistance training programmes for 12 weeks, 3× per week (LowR, n = 9, age 74 ± 5 years; HighR, n = 8, age 68 ± 6 years). Patellar tendon properties (stiffness [K], Young's modulus [YM], cross-sectional area [T CSA], and tendon length [T L]) were measured pre and post training using a combination of magnetic resonance imaging (MRI), B-mode ultrasonography, dynamometry, electromyography and ramped isometric knee extensions. With training K showed no significant change in the LowR group while it incremented by 57.7 % in the HighR group (p < 0.05). The 51.1 % group difference was significant (p < 0.05). These differences were still apparent when the data was normalized for T CSA and T L, i.e., significant increase in YM post-intervention in HighR (p < 0.05), but no change in LowR. These findings suggest that when prescribing exercise for a mixed genders elderly population, exercise intensities of ≤40 % 1RM may not be sufficient to affect tendon properties.

TGF-ß-superfamily signaling regulates embryonic stem cell heterogeneity: self-renewal as a dynamic and regulated equilibrium.

Embryonic stem cells dynamically fluctuate between phenotypic states, as defined by expression levels of genes such as Nanog, while remaining pluripotent. The dynamic phenotype of stem cells is in part determined by gene expression control and dictated by various signaling pathways and transcriptional regulators. We sought to define the activities of two TGF-ß-related signaling pathways, bone morphogenetic protein (BMP) and Nodal signaling, in modulating mouse embryonic stem (ES) cell heterogeneity in undifferentiated culture conditions. Both BMP and Nodal signaling pathways were seen to be active in distinct Nanog subpopulations, with subtle quantitative differences in activity. Pharmacological and genetic modulation of BMP or Nodal signaling strongly influenced the heterogeneous state of undifferentiated ES cells, as assessed by dynamic expression of Nanog reporters. Inhibition of Nodal signaling enhanced BMP activity, which through the downstream target Id factors, enhanced the capacity of ES cells to remain in the Nanog-high epigenetic state. The combined inhibition of Nodal and BMP signaling resulted in the accumulation of Nanog-negative cells, even in the presence of LIF, uncovering a shared role for BMP and Nodal signaling in maintaining Nanog expression and repression of differentiation. These results demonstrate a complex requirement for both arms of TGF-ß-related signaling to influence the dynamic cellular phenotype of undifferentiated ES cells in serum-based media, and that differing subpopulations of ES cells in heterogeneous culture have distinct responses to these signaling pathways. Several pathways, including BMP, Nodal, and FGF signaling, have important regulatory function in defining the steady-state distribution of heterogeneity of stem cells.

Transforming growth factor-beta superfamily in mouse embryonic stem cell self-renewal.

Embryonic stem (ES) cells are pluripotent cells that maintain the capability of undifferentiated self-renewal in culture. As mouse ES cells have the capacity to give rise to all the tissues of the body, they are an excellent developmental biology model system and a model for regenerative therapies. The extracellular cues and the intracellular signaling cascades that regulate ES cell self-renewal and cell-fate choices are complex and actively studied. Many developmental signaling pathways regulate the ES cell phenotype, and their intracellular programs interact to modulate the gene networks controlling ES cell pluripotency. This review focuses on the current understanding and outstanding questions of the roles of the transforming growth factor-beta-related signaling pathways in regulating pluripotency and differentiation of mouse ES cells. The complex dichotomic roles of bone morphogenetic protein signaling in maintaining the undifferentiated state and also inducing specific cell fates will be reviewed. The emerging roles of Nodal signaling in ES cell self-renewal will also be discussed.

Patellar tendon properties with fluctuating menstrual cycle hormones.

Debate continues over whether skeletal muscle performance and injury risk vary over the course of the menstrual cycle. Alterations in tendon properties may play a role in the potential fluctuations of both of these variables. The aim of the current study was to determine any association between menstrual cycle phase and corresponding levels of female sex hormones and tendon properties. Fifteen normally menstruating (28-32-day cycles) healthy females (age 23 +/- 1 years, mass 63.1 +/- 2.6 kg, height 1.66 +/- 0.02 m) not taking any form of hormonal contraceptive took part in this study. In vivo patellar tendon properties and associated circulating hormonal levels were assessed on 3 occasions including days 3 +/- 0.4, 13 +/- 0.2, and 21 +/- 0.3. Dynamometry, ultrasonography, electromyography, and biochemical assessment of circulating levels of estradiol and progesterone were utilized. No significant differences were seen in tendon mechanical properties among the 3 phases of the menstrual cycle (p > 0.05). Regressions were carried out and revealed that estrogen and maximal voluntary tendon force explained 17.8% (p = 0.043) of the variance in young's modulus. Our findings link estrogen to a chronic, rather than an acute, impact on tendon behavior. These findings are relevant to clinical outcomes, exercise performance, and injury risk. In terms of tendon properties, menstrual cycle phase does not necessarily need to be considered when organizing training and competition schedules.

Effect of acute tensile loading on gender-specific tendon structural and mechanical properties.

Stretching is commonly used prior to exercise, as it is thought to reduce the risk of injury, and it is also used in the preconditioning of tendon grafts. As tendon properties have been shown to be different between genders, it is proposed that stretching will differentially affect the structure. Here we examine the effect of acute stretch on the mechanical properties of both male and female medial gastrocnemius tendon. Female [20 years +/- 1 (SEM), n = 17] and male (22 years +/- 1, n = 18) subjects underwent a 5-min passive dorsiflexion stretch. Prior to and post stretch medial gastrocnemius tendon stiffness (K), length (l) and cross-sectional area (csa) were measured using ultrasonography and dynamometry. Stiffness and Young's modulus (epsilon) were significantly reduced with stretch for both genders (p < 0.05). Females showed significantly (p < 0.05) greater pre- to poststretch decreases in K (22.4 vs. 8.8%) and epsilon (20.5 vs. 8.4%) in comparison to males. The present results show that stretching acutely reduces stiffness of the medial gastrocnemius tendon in females and males, with females showing significantly greater change. The observed disparity between genders may be due in part to variations in tendon moment arm and intrinsic differences in tendon composition. These differential changes in tendon mechanical properties have functional, motor control, and injury risk implications, as well as possible implications for preconditioning of tendon grafts.

Plyometric vs. isometric training influences on tendon properties and muscle output.

The purpose of this study was to concurrently determine the effect that plyometric and isometric training has on tendon stiffness (K) and muscle output characteristics to compare any subsequent changes. Thirteen men trained the lower limbs either plyometrically or isometrically 2-3 times a week for a 6-week period. Medial gastrocnemius tendon stiffness was measured in vivo using ultrasonography during ramped isometric contractions before and after training. Mechanical output variables were measured using a force plate during concentric and isometric efforts. Significant (p < 0.05) training-induced increases in tendon K were seen for the plyometric (29.4%; 49.0 +/- 10.8 to 63.4 +/- 9.2 N x mm(-1)) and isometric groups (61.6%; 43.9 +/- 2.5 to 71.0 +/- 7.4 N x mm(-1)). Statistically similar increases in rate of force development and jump height were also seen for both training groups, with increases of 18.9 and 58.6% for the plyometric group and 16.7 and 64.3% for the isometric group, respectively. Jump height was found to be significantly correlated with tendon stiffness, such that stiffness could explain 21% of the variance in jump height. Plyometric training has been shown to place large stresses on the body, which can lead to a potential for injury, whereas explosive isometric training has been shown here to provide similar benefits to that of plyometric training with respect to the measured variables, but with reduced impact forces, and would therefore provide a useful adjunct for athletic training programs within a 6-week time frame.