Implication of SPARC in the modulation of the extracellular matrix and mitochondrial function in muscle cells

Abstract

Secreted protein, acidic and rich in cysteine (SPARC) is differentially associated with cell proliferation and extracellular matrix (ECM) assembly. We show here the effect of exogenous SPARC inhibition/induction on ECM and mitochondrial proteins expression and on the differentiation of C2C12 cells. The cells were cultured in growth medium (GM) supplemented with different experimental conditions. The differentiation of myoblasts was studied for 5 days, the expressions of ECM and mitochondrial proteins were measured and the formation of the myotubes was quantified after exogenous induction/inhibition of SPARC. The results indicate that the addition of recombinant SPARC protein (rSPARC) in cell culture medium increased the differentiation of C2C12 myoblasts and myogenin expression during the myotube formation. However, the treatment with antibody specific for SPARC (anti-SPARC) prevented the differentiation and decreased myogenin expression. The induction of SPARC in the proliferating and differentiating C2C12 cells increased collagen 1a1 protein expression, whereas the inhibition decreased it. The effects on fibronectin protein expression were opposite. Furthermore, the addition of rSPARC in C2C12 myoblast increased the expression of mitochondrial proteins, ubiquinol-cytochrome c reductase core protein II (UQCRC2) and succinate dehydrogenase iron-sulfur subunit (SDHB), whereas the anti-SPARC decreased them. During the differentiation, only the anti-SPARC had the effects on mitochondrial proteins, NADH dehydrogenase ubiquinone 1 beta subcomplex subunit 8 (NADHB8), SDHB and cytochrome c oxidase 1 (MTCO1). Thus, SPARC plays a crucial role in the proliferation and differentiation of C2C12 and may be involved in the link between the ECM remodeling and mitochondrial function.

Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

“…Similar to IL-15 and irisin, the expression of osteonectin (also known as SPARC) can be induced by exercise [ 99 ]. Current studies have only uncovered the activities of osteonectin in undifferentiated myoblasts, where it upregulated mitochondrial proteins such as ubiquinol-cytochrome c reductase core protein II (UQCRC2) and succinate dehydrogenase subunit (SDHB) probably through AMPK activation [ 100 , 101 ]. This osteonectin-dependent elevation of mitochondrial protein is important to myogenesis [ 100 ].…”

“…Current studies have only uncovered the activities of osteonectin in undifferentiated myoblasts, where it upregulated mitochondrial proteins such as ubiquinol-cytochrome c reductase core protein II (UQCRC2) and succinate dehydrogenase subunit (SDHB) probably through AMPK activation [ 100 , 101 ]. This osteonectin-dependent elevation of mitochondrial protein is important to myogenesis [ 100 ]. Because no study on the role of osteonectin in post-exercise skeletal muscle has been performed, the action mechanism of this myokine in mitochondrial adaptation remains unknown.…”

Secreted Protein Acidic and Rich in Cysteine as A Regeneration Factor: Beyond the Tissue Repair

“…In this context, SPARC has been shown to be implicated in a variety of metabolic functions, such as glucose tolerance improvement [ 34 ], while it is also required for both glucose homeostasis maintenance and insulin secretion [ 35 ]. In the skeletal muscle, SPARC also seems to act towards improved metabolic properties and functions [ 18 , 24 ], including mitochondrial functions [ 30 , 36 , 37 ], which is of interest knowing the importance of the mitochondria during regeneration [ 38 , 39 ]. Importantly, our latest study suggests that exercise-induced muscle phenotype changes are SPARC-dependent [ 40 ].…”

Comparative Transcriptome Profile Analysis of Longissimus dorsi Muscle Tissues From Two Goat Breeds With Different Meat Production Performance Using RNA-Seq

“…For example, the inhibition of SPARC led to a decrease in the diameter of myofibers ( Nakamura et al, 2013 ). SPARC also promotes the differentiation of C2C12 myoblasts during the myotube formation ( Melouane et al, 2018 ). CCDC80 has been reported to have a positive role in human skeletal myotubes differentiation ( Raymond et al, 2010 ).…”