ZAKß is activated by cellular compression and mediates contraction-induced MAP kinase signaling in skeletal muscle.

Mechanical inputs give rise to p38 and JNK activation, which mediate adaptive physiological responses in various tissues. In skeletal muscle, contraction-induced p38 and JNK signaling ensure adaptation to exercise, muscle repair, and hypertrophy. However, the mechanisms by which muscle fibers sense mechanical load to activate this signaling have remained elusive. Here, we show that the upstream MAP3K ZAKß is activated by cellular compression induced by osmotic shock and cyclic compression in vitro, and muscle contraction in vivo. This function relies on ZAKß's ability to recognize stress fibers in cells and Z-discs in muscle fibers when mechanically perturbed. Consequently, ZAK-deficient mice present with skeletal muscle defects characterized by fibers with centralized nuclei and progressive adaptation towards a slower myosin profile. Our results highlight how cells in general respond to mechanical compressive load and how mechanical forces generated during muscle contraction are translated into MAP kinase signaling.

Larger interface area at the human myotendinous junction in type 1 compared with type 2 muscle fibers.

The myotendinous junction (MTJ) is structurally specialized to transmit force. The highly folded muscle membrane at the MTJ increases the contact area between muscle and tendon and potentially the load tolerance of the MTJ. Muscles with a high content of type II fibers are more often subject to strain injury compared with muscles with type I fibers. It is hypothesized that this is explained by a smaller interface area of MTJ in type II compared with type I muscle fibers. The aim was to investigate by confocal microscopy whether there is difference in the surface area at the MTJ between type I and II muscle fibers. Individual muscle fibers with an intact MTJ were isolated by microscopic dissection in samples from human semitendinosus, and they were labeled with antibodies against collagen XXII (indicating MTJ) and type I myosin (MHCI). Using a spinning disc confocal microscope, the MTJ from each fiber was scanned and subsequently reconstructed to a 3D-model. The interface area between muscle and tendon was calculated in type I and II fibers from these reconstructions. The MTJ was analyzed in 314 muscle fibers. Type I muscle fibers had a 22% larger MTJ interface area compared with type II fibers (p < 0.05), also when the area was normalized to fiber diameter. By the new method, it was possible to analyze the structure of the MTJ from a large number of human muscle fibers. The finding that the interface area between muscle and tendon is higher in type I compared with type II fibers suggests that type II fibers are less resistant to strain and therefore more susceptible to injury.

The role of 18F-FDG PET/CT in the diagnosis of frozen shoulder.

PURPOSE: Frozen shoulder is characterized by pain and reduced passive movement capability, and the diagnose is made clinically. However, pain is the major symptom in the first stage before stiffness occurs, and the condition can be mistaken for subacromial impingement. This study explored the possibility to use positron emission tomography/computed tomography (PET/CT) with a 18F Flour-Deoxy-Glucose (FDG) tracer in the diagnostic process. METHODS: Eleven patients with frozen shoulder and 9 patients with subacromial impingement received a 18F-FDG PET/CT scan before being treated surgically. During arthroscopy, the diagnoses were confirmed. Images were blindly analyzed visually by two nuclear medicine physicians. Also, semi-quantified analysis applying a set of standard regions was performed, and standard uptake value in both shoulder regions was recorded. RESULTS: Both the visual description of the pictures and the semi-quantified analysis generally showed increased FDG uptake in the affected shoulder regions of patients that had frozen shoulder and no uptake in patients with subacromial impingement. Kappa for interobserver agreement in the visual assessments was 0.74. Sensitivity was 92% and specificity 93% of the visual assessment, 77% and 93%, respectively, of the semi-quantified analyses, and by combining the two types of analyses sensitivity was 100% and specificity was 93% for the distinction between frozen shoulders and subacromial impingement/unaffected shoulders. CONCLUSION: 18F-FDG PET/CT seems to be a valid method to diagnose frozen shoulder. This is clinically relevant in diagnostically challenging cases, for instance in the first phase of frozen shoulder, which can be difficult to distinguish from subacromial impingement. LEVEL OF EVIDENCE: II.

The Myotendinous Junction-A Vulnerable Companion in Sports. A Narrative Review.

The incidence of strain injuries continues to be high in many popular sports, especially hamstring strain injuries in football, despite a documented important effect of eccentric exercise to prevent strains. Studies investigating the anatomical properties of these injuries in humans are sparse. The majority of strains are seen at the interface between muscle fibers and tendon: the myotendinous junction (MTJ). It has a unique morphology with a highly folded muscle membrane filled with invaginations of collagen fibrils from the tendon, establishing an increased area of force transmission between muscle and tendon. There is a very high rate of remodeling of the muscle cells approaching the MTJ, but little is known about how the tissue adapts to exercise and which structural changes heavy eccentric exercise may introduce. This review summarizes the current knowledge about the anatomy, composition and adaptability of the MTJ, and discusses reasons why strain injuries can be prevented by eccentric exercise.