Mitochondrial proteolysis is an evolutionarily conserved quality-control mechanism to maintain proper mitochondrial integrity and function. However, the physiological relevance of stress-induced impaired mitochondrial protein quality remains unclear. Here, we demonstrate that LONP1, a major mitochondrial protease resides in the matrix, plays a role in controlling mitochondrial function as well as skeletal muscle mass and strength in response to muscle disuse. In humans and mice, disuse-related muscle loss is associated with decreased mitochondrial LONP1 protein. Skeletal muscle-specific ablation of LONP1 in mice resulted in impaired mitochondrial protein turnover, leading to mitochondrial dysfunction. This caused reduced muscle fiber size and strength. Mechanistically, aberrant accumulation of mitochondrial-retained protein in muscle upon loss of LONP1 induces the activation of autophagy-lysosome degradation program of muscle loss. Overexpressing a mitochondrial-retained mutant ornithine transcarbamylase (ΔOTC), a known protein degraded by LONP1, in skeletal muscle induces mitochondrial dysfunction, autophagy activation, and cause muscle loss and weakness. Thus, these findings reveal a role of LONP1-dependent mitochondrial protein quality-control in safeguarding mitochondrial function and preserving skeletal muscle mass and strength, and unravel a link between mitochondrial protein quality and muscle mass maintenance during muscle disuse.
Background The regeneration of muscle cells from stem cells is an intricate process, and various genes are included in the process such as myoD, mf5, mf6, etc. The key genes and pathways in the differentiating stages are various. Therefore, the differential expression of key genes after 4 weeks of differentiation were investigated in our study. Method Three published gene expression profiles, GSE131125, GSE148994, and GSE149055, about the comparisons of pluripotent stem cells to differentiated cells after 4 weeks were obtained from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (DEGs) were obtained for further analysis such as protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA analysis. After hub genes and key pathways were obtained, we manipulated in vitro cell research for substantiation such as immunohistochemical staining and semi-quantitative analysis and quantitative real-time PCR. Results A total of 824 DEGs including 350 upregulated genes and 474 downregulated genes were identified in the three GSEs. Nineteen hub genes were identified from the PPI network. The GO and KEGG pathway analyses confirmed that myogenic differentiation at 4 weeks was strongly associated with pathway in cancer, PI3K pathway, actin cytoskeleton regulation and metabolic pathway, biosynthesis of antibodies, and cell cycle. GSEA analysis indicated the differentiated cells were enriched in muscle cell development and myogenesis. Meanwhile, the core genes in each pathway were identified from the GSEA analysis. The in vitro cell research revealed that actin cytoskeleton and myoD were upregulated after 4-week differentiation. Conclusions The research revealed the potential hub genes and key pathways after 4-week differentiation of stem cells which contribute to further study about the molecular mechanism of myogenesis regeneration, paving a way for more accurate treatment for muscle dysfunction.
Purpose: This study aims to clarify the systems underlying regulation and regulatory roles of hydrogen in the myogenic differentiation of adipose mesenchymal stem cells (ADSCs). Materials and methods: In this study, ADSCs acted as an in vitro myogenic differentiating mode. First, the Alamar blue Staining and mitochondrial tracer technique were used to verify whether hydrogen could promote cell proliferation. In addition, this study assessed myogenic differentiating markers (e.g., Myogenin, Mhc and Myod protein expressions) based on the Western blotting assay, analysis on cellular morphological characteristics (e.g., Myotube number, length, diameter and maturation index), RT-PCR (Mhc and Myod mRNA expression) and Immunofluorescence analysis (Desmin, Myosin and β-actin protein expression). Lastly, to verify the myogenic differentiating system of hydrogen, Western blotting assay was performed to detect p38 and p-p38 proteins expressions. Results: Hydrogen can remarkably enhance the proliferation of ADSCs in vitro by increasing the number of single-cell mitochondria and by up-regulating the expression of myogenic biomarkers (e.g., Myod, Mhc and myotube formation). The expressions of both p38 and p-p38 were up-regulated by hydrogen. The differentiating ability was suppressed when the cells were cultivated in combination with SB203580 (p38 MAPK signal pathway inhibitor). Conclusions: The present study initially indicated that hydrogen can promote myogenic differentiation via the p38 MAPK pathway. Thus, the mentioned results present insights into myogenic differentiation and are likely to generate one potential alternative strategy for skeletal muscle related diseases.
Magnolol is the active component of the traditional Chinese medicine Magnolia officinalis, and has antioxidant, anti-inflammatory and anticancer activities, as well as an effect on bone metabolism in vitro. In the present study, it is reported that magnolol suppresses osteoclastogenesis in vivo and in vitro. Magnolol prevented ovariectomy-induced bone loss and osteoclastogenesis in vivo, and decreased the serum levels of C-terminal telopeptide of type 1 collagen, interleukin-6, tumor necrosis factor (TNF)-α and tartrate-resistant acid phosphatase 5B. In vitro, magnolol inhibited the osteoclastogenesis induced by the receptor activator for nuclear factor-κB ligand, and impaired the osteoclast function in bone marrow monocytes and RAW264.7 cells in a dose-dependent manner. Furthermore, magnolol suppressed the expression levels of the osteoclastogenesis markers cathepsin K, calcitonin receptor, matrix metalloproteinase 9, TNF receptor-associated factor 6 and tartrate-resistant acid phosphatase by inhibiting the nuclear factor-κB and mitogen-activated protein kinase pathways. Therefore, magnolol is a promising agent for the treatment of osteoporosis and associated disorders.
Background: Acute skeletal muscle injuries are common among physical or sports traumas. The excessive oxidative stress at the site of injury impairs muscle regeneration. The authors have recently developed porous Se@SiO2 nanoparticles (NPs) with antioxidant properties. Methods: The protective effects were evaluated by cell proliferation, myogenic differentiation and mitochondrial activity. Then, the therapeutic effect was investigated in a cardiotoxin-induced muscle injury rat model. Results: Porous Se@SiO2 NPs significantly protected the morphological and functional stability of mitochondria, thus protecting satellite cells from H2O2-induced damage to cell proliferation and myogenic differentiation. In the rat model, intervention with porous Se@SiO2 NPs promoted muscle regeneration. Conclusion: This study reveals the application potential of porous Se@SiO2 NPs in skeletal muscle diseases related to mitochondrial dysfunction.
Background: The adipose-derived stem cells (ADSCs) have been proved to be effective in the myogenic differentiation with the 5-Aza induction. However, the induction procedure definitly decreased the proliferation ability of ADSCs. The platelet-rich plasma (PRP), famous of its proliferating abilities, is widely used in the field of tissue regeneration. The purpose of this study is to determine the efficacy and mechanism of PRP on the myogenic differentiation process.Method: The published gene expression profile, GSE 70918, which compared the efficacy of PRP and platelet-rich plasma (PPP) on the tendon fibroblast was obtained from the Gene Expression Omnibus (GEO) database.The further protein‑protein interaction (PPI) network Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was performed based on differentially epressed genes(DEGs). Furethermore, the micro-RNA-mRNA interaction network was analyzed and visualized by cytoscape. Finally, the in vitro experimental cell research was performed to certify the efficay of PRP on myogenic differentiation.Results: From our analysis, 148 DEGs, 87 up-regulated and 61 down-regulated, were obtained from the gene profile. The PPI network showed that the inflammatory factors as IL-1A, CXCL, CXCR etc. were significantly down-regulated and the muscle functional related genes as MYLC and MYO7A were significantly up-regulated. The GO and KEGG analysis demonstrated that up-regulated DEGs were enriched in focal adhesion, dilated cardiomyopathy, hypertrophic cardiomyopathy and calcium signaling pathway which were correlated to muscle function. Meanwhile, the microRNA-mRNA interaction network were estabilished based on DEGs. The in vitro experimental showed that PRP can significantly increase the proliferation ability of ADSCs during myogenic introduction and increase the expression of troponin and myosin which were correlate to the function of mature muscle.Conclusions:The research showed that PRP is an effective way to enhance the proliferation ability during the myogenic differentiation and increase the expression of muscle functional related protein.
Purpose: The study aims to determine the process of myoginc differentiation in human pluripotent stem cells and to figure out that the key pathways and hub genes in the process, which do helpful for the further research of muscular regeneration.Method: Three gene expression profiles, GSE131125, GSE148994, GSE149055, about the comparisons of pluripotent stem cells and myogenic stem cells from the Gene Expression Omnibus (GEO) data base. Common differentially expressed genes (DEGs) were obtained and for the further analysis as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA analysis and protein‑protein interaction (PPI) network. In vitro cell research to verify the hub genes and key pathways.Result:824 DEGs were co-expressed in the three GSEs. 19 hub genes were identified from the PPI network. The GO and KEGG pathway analysis were performed to determine the functions of DEGs. GSEA analysis indicated the differentiated cells were enriched in muscle cell development and myogenesis.Conclusion: Our research revealed the main hub genes and modules in the myogeinc process of stem cells which contribute to further study about the molecular mechanism of myogenesis regeneration. Paving a way for more accurate treatment for muscle dysfunction.
Background The inferior glenohumeral ligament (IGHL) plays an important role in maintaining shoulder joint stability. However, no systematic studies on shoulder stability and function of patients with FS after IGHL release exist. This study assessed the functional and clinical outcomes of IGHL release for FS.Methods Forty-seven patients underwent arthroscopic capsule and IGHL release with the same postoperative rehabilitation procedure. Five functional parameters were measured postoperatively at 4, 8, 12 and 28 weeks: the apprehension test result, American Shoulder and Elbow Surgeons Score (ASES), Constant score, visual analog scale (VAS) score and active range of motion (ROM).Results All patients improved in the aforementioned evaluations. At 28 weeks, the ASES, Constant score and VAS score improved from 31.30±6.41 to 92.43±3.89, 30.15±6.85 to 90.71±4.27 and 6.73±0.72 to 0.60±0.74, respectively (p<0.05). Forward flexion (FF) and abduction (ABD) improved from 73.85±14.94 to 166.70±7.23 and from 69.65±12.74 to 165.03±6.36, respectively (p<0.05). External rotation (ER) and internal rotation (IR) also significantly improved. In total, 95% of the patients were able to perform full elevation, and 97.5% of the patients could place the dorsum of their hands between their shoulder blades. All patients had negative apprehension tests, and no dislocations occurred. No other serious postoperative complications were observed.Conclusions Arthroscopic capsule and IGHL release was effective and could improve the active ROM and relieve pain in patients with FS. This surgical procedure did not cause instability or dislocations in the shoulder joint.
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