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The skeletal muscle mass accounts for more than 40% of the body weight of healthy adults. The skeletal muscle not only plays an important role in physical activities but also affects the function of other organs as a secretory organ secreting multiple muscle factors. Therefore, it is important to maintain the normal quantity and function of skeletal muscle. Skeletal muscle mass is the basis of skeletal muscle function and is often affected by many factors such as exercise and disease. Resistance exercise training induces increased protein synthesis in skeletal muscle cells, while limb disuse, chronic obstructive pulmonary disease, heart failure, chronic kidney disease, cachexia, Duchenne muscular dystrophy and many other pathological conditions lead to decreased protein synthesis or enhanced protein degradation of skeletal muscle cells. The process of skeletal muscle hypertrophy involves changes in multiple signaling pathways, such as IGF-1/PI3K/Akt, myostatin and G protein. On the other hand, activations of the ubiquitin-proteasome system, IGF-1/Akt/FoxO, autophagy-lysosomal pathway, NF-κB, and the glucocorticoid-mediated signaling pathways play important roles in regulating muscle atrophy. These signaling pathways regulate skeletal muscle mass and are modulated by some different conditions. This review briefly summarizes the signaling pathways of skeletal muscle mass control.

Insulin resistance is a common pathophysiological mechanism of obesity and type 2 diabetes mellitus. Skeletal muscle is one of the major target organs of insulin-mediated glucose uptake, metabolism and utilization, and it is the earliest and most important site of insulin resistance. Studies have shown that the impairments of glucose uptake, insulin signaling pathway and mitochondrial biosynthesis are closely related to skeletal muscle insulin resistance. When insulin resistance develops in skeletal muscle, multiple microRNAs (miRNAs) are up-regulated (miR-106b, miR-23a, miR-761, miR-135a, Let-7 and miR-29a) or down-regulated (miR-133a, miR-149 and miR-1). They participate in the regulation of skeletal muscle glucose uptake, insulin signaling pathway and mitochondrial biogenesis, and thus play important roles in the occurrence and development of skeletal muscle insulin resistance. Therefore, these miRNAs may serve as potential targets for the treatment of skeletal muscle insulin resistance or diabetes.

The decline in skeletal muscle mass and function with age is referred as sarcopenia. It is characterized by the muscle fiber's quality, strength, muscle endurance and metabolic ability decreasing as well as the fat and connective tissue growing. Previous studies have shown that sarcopenia in itself features decreased number and cross-sectional area of muscle fibers and the net degradation of protein, which results from the joint effects of multiple factors such as the exacerbation of inflammation, oxidative stress injury, mitochondrial dysfunction, abnormal autophagy and dysregulation of muscle quality regulatory factors. In this review, we systematically displayed the molecular mechanism of sarcopenia, which will be helpful to deepen our understanding of sarcopenia and provide potential targets for the prevention and treatment of sarcopenia.

The objective of this study was to explore the roles of macrophages in the regeneration of injured skeletal muscle and the mechanisms involved. Mice were randomly divided into the following groups: muscle contusion (S), muscle contusion control (S Con ), macrophages depleted (T) and macrophages depleted control (T Con ) groups. Muscle contusion model was created by high-energy blunt injury. Macrophages depletion model was constructed by injection of clodronate-liposomes. Their gastrocnemius muscles were harvested at the time points of 1, 3, 7 and 14 d post-injury. The changes in skeletal muscle morphology were assessed by hematoxylin-eosin (HE) staining and Masson's trichrome staining. The mRNA and protein levels of inflammatory cytokines, chemokines and oxidative stress factors were analyzed by real-time polymerase chain reaction (RCR) and Western blotting, respectively. HE staining results showed that a small amount of regenerating myofibers were observed in the S group (14 d post-injury), whereas a large number of regenerating muscle fibers were observed in the T group. Quantitative analyses showed that the sizes of regenerating myofibers were significantly smaller in the T group as compared with the S group at 14 d post-injury (P < 0.05). At the same time, Masson staining results showed that macrophage depletion significantly increased the area of fibrosis as compared with the S group at 14 d post-injury (P < 0.01). The expression levels of inflammatory cytokines, chemokines, and oxidative stress factors were increased significantly after muscle injury. Moreover, macrophage depletion increased the expressions of inflammatory cytokines, chemokines and oxidative stress factors as compared with the S group during the later stage of injury (7-14 d post-injury). These results suggest that macrophages depletion can aggravate fibrosis and impair muscle regeneration, and inflammatory cytokines, chemokines and oxidative stress factors may be involved in this process.

Under normal condition, there are a few lipid droplets in skeletal muscle. But in skeletal muscle acute injury, muscular dystrophy, muscle atrophy, obesity, diabetes and other pathological conditions, the fat deposition in skeletal muscle increases, which implicate that the fat deposition may play an important role in the pathogenesis of these diseases. However, the mechanisms of development and regulation of fat deposition in skeletal muscle are not clear. Clarifying the key signaling pathways and regulatory factors that affect fat deposition in skeletal muscle, and exploring new ways to improve the fat deposition in skeletal muscle will not only help to deepen our understanding of the pathogenesis of these diseases, but also provide new ideas for the treatment of these diseases. This paper reviews the research progresses and main mechanisms of fat deposition in skeletal muscle.

Skeletal muscle repair after injury includes three stages which are inflammation, repair and tissue remodeling. The ability of Skeletal muscle to regenerate in response to injury is solely dependen on the activation, proliferation and differentiation of satellite cells. After skeletal muscle injury, hepatocyte growth factor (HGF) can regular muscle satellite cell function in the manner of autocrine, paracrine or endocrine, thus affecting the regeneration of damaged skeletal muscle. Studies about the mechanism have shown that HGF may bind to its receptor, e-met, to start the relevant signaling pathways involved in skeletal muscle satellite cell activation, proliferation, differentiation and migration, which affects skeletal muscle regeneration process.

Background: Cutaneous tactile allodynia, or painful hypersensitivity to mechanical stimulation of the skin, is typically associated with neuropathic pain, although also present in chronic pain patients who do not have evidence of nerve injury. We examine whether deep tissue microvascular dysfunction, a feature common in chronic non-neuropathic pain, contributes to allodynia., Results: Persistent cutaneous allodynia is produced in rats following a hind paw ischemia-reperfusion injury that induces microvascular dysfunction, including arterial vasospasms and capillary slow flow/no-reflow, in muscle. Microvascular dysfunction leads to persistent muscle ischemia, a reduction of intraepidermal nerve fibers, and allodynia correlated with muscle ischemia, but not with skin nerve loss. The affected hind paw muscle shows lipid peroxidation, an upregulation of nuclear factor kappa B, and enhanced pro-inflammatory cytokines, while allodynia is relieved by agents that inhibit these alterations. Allodynia is increased, along with hind paw muscle lactate, when these rats exercise, and is reduced by an acid sensing ion channel antagonist., Conclusion: Our results demonstrate how microvascular dysfunction and ischemia in muscle can play a critical role in the development of cutaneous allodynia, and encourage the study of how these mechanisms contribute to chronic pain. We anticipate that focus on the pain mechanisms associated with microvascular dysfunction in muscle will provide new effective treatments for chronic pain patients with cutaneous tactile allodynia.