Unravelling the Effects of Syndecan-4 Knockdown on Skeletal Muscle Functions

Abstract

The remodelling of the extracellular matrix plays an important role in skeletal muscle development and regeneration. Syndecan-4 is a cell surface proteoglycan crucial for muscle differentiation. Syndecan-4−/− mice have been reported to be unable to regenerate following muscle damage. To investigate the consequences of the decreased expression of Syndecan-4, we have studied the in vivo and in vitro muscle performance and the excitation–contraction coupling machinery in young and aged Syndecan-4+/− (SDC4) mice. In vivo grip force was decreased significantly as well as the average and maximal speed of voluntary running in SDC4 mice, regardless of their age. The maximal in vitro twitch force was reduced in both EDL and soleus muscles from young and aged SDC4 mice. Ca2+ release from the sarcoplasmic reticulum decreased significantly in the FDB fibres of young SDC4 mice, while its voltage dependence was unchanged regardless of age. These findings were present in muscles from young and aged mice as well. On C2C12 murine skeletal muscle cells, we have also found altered calcium homeostasis upon Syndecan-4 silencing. The decreased expression of Syndecan-4 leads to reduced skeletal muscle performance in mice and altered motility in C2C12 myoblasts via altered calcium homeostasis. The altered muscle force performance develops at an early age and is maintained throughout the life course of the animal until old age.

Migration of Myogenic Cells Is Highly Influenced by Cytoskeletal Septin7

“…The front-rear polarity should be maintained during migration, because this biochemical process is required to block the formation of lamellipodia at the trailing edges [46,48,49]. Here, we show that resting [Ca 2+ ] i is not significantly different in Ctrl, Scr, and KD myoblasts; however, upon activation the migrating cells have increased [Ca 2+ ] i , as it has been proven recently in C2C12 cells with a decreased expression of cell surface protein Syndecan-4 [50]. Interestingly, this elevation in [Ca 2+ ] i is significantly lower in migrating KD cells compared to that of their control counterparts, which might be related to Septin7 depletion.…”

Syndecan-4 is required for early-stage repair responses during zebrafish heart regeneration

“…A previous study showed that SDC4 was required to maintain the proliferation ability of skeletal muscle cells [ 18 ]. However, it is not known whether SDC4 regulates cell proliferation and migration during heart regeneration.…”

Characterization of wooden breast myopathy: a focus on syndecans and ECM remodeling

“…The syndecan family includes four members (syndecan-1, -2, -3, and -4) that are differentially expressed in various tissues and cell types ( Lambaerts et al, 2009 ; Velleman, 2012 ). Syndecans play critical roles in cell adhesion, proliferation, differentiation, migration, and survival ( Couchman et al, 2015 ) and are important for skeletal muscle growth, health, and aging ( Pisconti et al, 2012 ; Rønning et al, 2015 ; Pisconti et al, 2016 ; Velleman and Song, 2017 ; Rønning et al, 2020 ; Sztretye et al, 2023 ). They also play a role in ECM remodeling and can act as co-receptors for growth factors, chemokines, and extracellular matrix molecules ( Xian et al, 2009 ; Couchman, 2010 ; Lunde et al, 2016 ).…”