The behaviour of T2*and T2 relaxation time in extrinsic foot muscles under continuous exercise: A prospective analysis during extended running

Objectives Previous studies on T2* and T2 relaxation time of the muscles have shown that exercise leads to an initial increase, presumably representing different intramuscular physiological processes such as increase in intracellular volume or blood oxygenation level dependent effects with a subsequent decrease after cessation of exercise. Their behaviour during prolonged exercise is still unknown but could provide important information for example about the pathophysiology of overuse injuries. The aim of this study was to evaluate the temporal course of T2* and T2 relaxation time in extrinsic foot muscles during prolonged exercise and determine the optimal mapping technique. Methods Ten participants had to run a total of 75 minutes at their individual highest possible running speed, with interleaved MR scans at baseline and after 2.5, 5, 10, 15, 45 and 75 minutes. The examined extrinsic foot muscles were manually segmented, and relaxation time were analysed regarding its respective time course. Results T2* and T2 relaxation time showed an initial increase, followed by a plateau phase between 2.5 and 15 minutes and a subsequent decrease. For the T2* relaxation time, this pattern was also apparent, but less pronounced, with more muscles not reaching significance (p<0.05) when comparing different time points. Conclusions T2* and T2 relaxation time showed a similar course with an initial rapid increase, a plateau phase and a subsequent decrease under prolonged exercise. Moderate but long-term muscular activity appears to have a weaker effect on T2* relaxation time than on T2 relaxation time

Plastin 3 in health and disease: a matter of balance

For a long time, PLS3 (plastin 3, also known as T-plastin or fimbrin) has been considered a rather inconspicuous protein, involved in F-actin-binding and -bundling. However, in recent years, a plethora of discoveries have turned PLS3 into a highly interesting protein involved in many cellular processes, signaling pathways, and diseases. PLS3 is localized on the X-chromosome, but shows sex-specific, inter-individual and tissue-specific expression variability pointing towards skewed X-inactivation. PLS3 is expressed in all solid tissues but usually not in hematopoietic cells. When escaping X-inactivation, PLS3 triggers a plethora of different types of cancers. Elevated PLS3 levels are considered a prognostic biomarker for cancer and refractory response to therapies. When it is knocked out or mutated in humans and mice, it causes osteoporosis with bone fractures; it is the only protein involved in actin dynamics responsible for osteoporosis. Instead, when PLS3 is upregulated, it acts as a highly protective SMN-independent modifier in spinal muscular atrophy (SMA). Here, it seems to counteract reduced F-actin levels by restoring impaired endocytosis and disturbed calcium homeostasis caused by reduced SMN levels. In contrast, an upregulation of PLS3 on wild-type level might cause osteoarthritis. This emphasizes that the amount of PLS3 in our cells must be precisely balanced; both too much and too little can be detrimental. Actin-dynamics, regulated by PLS3 among others, are crucial in a lot of cellular processes including endocytosis, cell migration, axonal growth, neurotransmission, translation, and others. Also, PLS3 levels influence the infection with different bacteria, mycosis, and other pathogens

The time course of calf muscle fluid volume during prolonged running

Muscle fluid is essential for the biochemistry and the biomechanics of muscle contraction. Here, we provide evidence that muscle fluid volumes undergo significant changes during 75 min of moderate intensity (2.7 +/- 0.4 m/s) running. Using MRI measurements at baseline and after 2.5, 5, 10, 15, 45 and 75 min, we found that the volumes of calf muscles (quantified through average cross-sectional area) in 18 young recreational runners increase (up to 9% in the gastrocnemii) at the beginning and decrease (below baseline levels) at later stages of running. However, the intensity of changes varied between analyzed muscles. We speculate that these changes are induced by muscle activity and dehydration-related changes in osmotic pressure gradients between intramuscular and extramuscular spaces. These findings highlight the complex nature of muscle fluid shifts during prolonged running exercise

The habitual motion path theory: Evidence from cartilage volume reductions in the knee joint after 75 minutes of running

The habitual motion path theory predicts that humans tend to maintain their habitual motion path (HMP) during locomotion. The HMP is the path of least resistance of the joints defined by an individual's musculoskeletal anatomy and passive tissue properties. Here we tested whether participants with higher HMP deviation and whether using footwear that increases HMP deviation during running show higher reductions of knee joint articular cartilage volume after 75 minutes of running. We quantified knee joint articular cartilage volumes before and after the run using a 3.0-Tesla MRI. We performed a 3D movement analysis of runners in order to quantify their HMP from a two-legged squat motion and the deviation from the HMP when running in different footwear conditions. We found significantly more cartilage volume reductions in the medial knee compartment and patella for participants with higher HMP deviation. We also found higher cartilage volume reductions on the medial tibia when runners wore a shoe that maximized their HMP deviation compared with the shoe that minmized their HMP deviation. Runners might benefit from reducing their HMP deviation and from selecting footwear by quantifying HMP deviation in order to minimize joint cartilage loading in sub-areas of the knee

Insights into extrinsic foot muscle activation during a 75 min run using T2 mapping

The extrinsic foot muscles are essentially for controlling the movement path but our knowledge of their behavior during prolonged running is still very limited. Therefore, this study analyzed the time-course of muscle activation using T2 mapping during 75 min of running. In this prospective study, 19 recreational active runners completed 75 min of treadmill running at a constant speed. Interleaved T2 mapping sequences were acquired and segmented at timepoints 0, 2.5, 5, 10, 15, 45, and 75 min. ANOVA for repeated measurements followed by a Tukey post hoc test and Pearson correlation between running speed and initial signal increase at 2.5 min were calculated. All muscles showed a significant signal increase between baseline and 2.5 min (e.g. medial gastrocnemius:+15.48%; p= 10 km/h). T2 relaxation times do not only decrease after cessation of exercise but already during prolonged running. The lesser initial increase and later decrease in faster runners may indicate training induced changes

Does footwear affect articular cartilage volume change after a prolonged run?

The aim of this study was to investigate knee intra-articular cartilage volume changes after a prolonged running bout in three footwear conditions. Twelve participants performed 75-minute running bouts in the three footwear conditions. Before and after each running bout, magnetic resonance imaging (MRI) scans were obtained using a high-resolution 3.0 Tesla MRI. Three-dimensional reconstruction of the cartilage plates of the patella, the femur, and the tibia was created to quantify cartilage volume change due to the 75-minute running bout. Three-dimensional biomechanical data were also collected using an integrated motion capture and force treadmill system. There were no statistically significant differences among shoe conditions for all anatomical regions. However, significant cartilage volume reductions at all anatomical sites were observed after the 75-minute running bout in each footwear condition. These data suggest that the intra-articular knee cartilage undergoes a significant reduction in cartilage volume during a prolonged run that may indicate an increase in joint loading. There was a considerable variation in cartilage volume between participants across footwear conditions indicating an individual cartilage volume response to footwear. An individualistic approach to footwear recommendations may help in minimizing this change in cartilage

Expression and Localization of Thrombospondins, Plastin 3, and STIM1 in Different Cartilage Compartments of the Osteoarthritic Varus Knee

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA