Myopathy Associated With Dermatan Sulfate-Deficient Decorin and Myostatin in Musculocontractural Ehlers-Danlos Syndrome: A Mouse Model Investigation

Carbohydrate sulfotransferase 14 (CHST14) encodes dermatan 4-O-sulfotransferase 1, a critical enzyme for dermatan sulfate (DS) biosynthesis. Musculocontractural Ehlers-Danlos syndrome (mcEDS) is associated with biallelic pathogenic variants of CHST14 and is characterized by malformations and manifestations related to progressive connective tissue fragility. We identified myopathy phenotypes in Chst14-deficient mice using an mcEDS model. Decorin is a proteoglycan harboring a single glycosaminoglycan chain containing mainly DS, which are replaced with chondroitin sulfate (CS) in mcEDS patients with CHST14 deficiency. We studied the function of decorin in the skeletal muscle of Chst14-deficient mice because decorin is important for collagen-fibril assembly and has a myokine role in promoting muscle growth. Although decorin was present in the muscle perimysium of wild-type (Chst14+/+) mice, decorin was distributed in the muscle perimysium as well as in the endomysium of Chst14–/– mice. Chst14–/– mice had small muscle fibers within the spread interstitium; however, histopathological findings indicated milder myopathy in Chst14–/– mice. Myostatin, a negative regulator of protein synthesis in the muscle, was upregulated in Chst14–/– mice. In the muscle of Chst14–/– mice, decorin was downregulated compared to that in Chst14+/+ mice. Chst14–/– mice showed altered cytokine/chemokine balance and increased fibrosis, suggesting low myogenic activity in DS-deficient muscle. Therefore, DS deficiency in mcEDS causes pathological localization and functional abnormalities of decorin, which causes disturbances in skeletal muscle myogenesis.

ROLE OF RESISTANCE EXERCISE IN CONTROLLING INSULIN-LIKE GROWTH FACTOR 1 (IGF-1) AND IT’S ASSOCIATION WITH METABOLIC DISEASE PREVENTION

Based on data Riset Kesehatan Dasar (Riskesdas) in 2007, the number of people who had no or low physical activity reached 48.2 %. This condition contributes to the increasing number of metabolic disease cases such as hypertension, heart disease, stroke, and diabetes mellitus. Optimizing training approaches especially the aerobic type helps to counter metabolic diseases. Unfortunately, the benefits of resistance training (RT) are less understood. RT improves muscle strength, induces muscle hypertrophy, improvement of local muscular performance, and also helps to strengthen body balance and coordination. There is an interplay between training and hormone in muscle adaptation during resistance training. The hormone plays an important role in the regeneration of muscle after resistance training. The changes in hormone level cause hypertrophy. Regeneration and muscle hypertrophy are mediated by activation, proliferation, and differentiation of satellite cells. It is regulated by mitotic and myogenic activity, namely insulin-like growth factor-1 (IGF-1), which serves as a paracrine or autocrine. A better understanding of homeostasis hormone during training in skeletal muscle and its ultimate purpose to counter metabolic disease will lead us to a better treatment approach for the patient.

Water-soluble fullerene-based nanostructures with promising antiviral and myogenic activity

A fullerene derivative with phosphonic acid residues demonstrated promising activity against ten different viruses and the ability to promote myogenic differentiation of stem cells.