Extracellular deposition of matrilin-2 controls the timing of the myogenic program during muscle regeneration

Abstract

BSTRACTHere, we identify a role for the matrilin-2 (Matn2) extracellular matrix protein in controlling the early stages of myogenic differentiation. We observed Matn2 deposition around proliferating, differentiating and fusing myoblasts in culture and during muscle regeneration in vivo. Silencing of Matn2 delayed the expression of the Cdk inhibitor p21 and of the myogenic genes Nfix, MyoD and Myog, explaining the retarded cell cycle exit and myoblast differentiation. Rescue of Matn2 expression restored differentiation and the expression of p21 and of the myogenic genes. TGF-b1 inhibited myogenic differentiation at least in part by repressing Matn2 expression, which inhibited the onset of a positive-feedback loop whereby Matn2 and Nfix activate the expression of one another and activate myoblast differentiation. In vivo, myoblast cell cycle arrest and muscle regeneration was delayed in Matn2 2/2 relative to wild-type mice. The expression levels of Trf3 and myogenic genes were robustly reduced in Matn2 2/2 fetal limbs and in differentiating primary myoblast cultures, establishing Matn2 as a key modulator of the regulatory cascade that initiates terminal myogenic differentiation. Our data thus identify Matn2 as a crucial component of a genetic switch that modulates the onset of tissue repair.

Syndecan‐4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition

“…Note, that both promyostatin and mature myostatin were detected in the supernatant (digestion buffer) after heparinase digestion. the earlier observed transient upregulation of SDC4 mRNA [5]. SDC4 is expressed ubiquitously; therefore, it may have originated not only from muscle but from other cell types (e.g.…”

“…By understanding the process of skeletal muscle regeneration we might have the possibility to improve it following sport injuries or during aging. Several studies described that proteoglycans and other components of the extracellular matrix are involved in tissue regeneration and skeletal muscle differentiation [4][5][6]. The crucial roles of syndecan (SDC) proteoglycans have been shown in the regeneration of the skin, vasculature and skeletal muscle [6].…”

Novel alternative splice variants of NFIX and their diverse mRNA expression patterns in dairy goat

“…Interestingly, we have found 3 different variants of goat NFIX that were expressed in the muscle tissue, of which NFIXa had the highest level of expression compared to the other two. Since NFIX was reported to regulate myogenic development of the embryo into fetus (Messina et al, 2010;Deák et al, 2014;Heng et al, 2014), we conclude that the main function of NFIX in muscles might be expressed through NFIXa.…”

Genetic contributions to precocity traits in racing Thoroughbreds

“…MATN2 has been shown to be a crucial component of a genetic switch that modulates the onset of tissue repair, in particular muscle regeneration (Deák et al . ; Korpos et al . ).…”