SPARC is up-regulated during skeletal muscle regeneration and inhibits myoblast differentiation
Stine Juhl Petersson1,2, Louise Helskov Jørgensen1, Ditte C. Andersen1,3,4, Rikke C. Nørgaard3, Charlotte Harken Jensen3,4 and Henrik Daa Schrøder1
1Department of Clinical Pathology, Institute of Clinical Research, University of Southern Denmark and Odense University Hospital, 2Department of Endocrinology, Section for Molecular Diabetes & Metabolism, Odense University Hospital and Institute of Clinical Research, University of Southern Denmark, 3Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark and 4Department of Clinical Biochemistry and Pharmacology, Odense University Hospital/Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark.
Offprint requests to: Henrik Daa Schrøder, Department of Clinical Pathology, Odense University Hospital, J.B. Winsloewsvej 15, 2nd floor, DK-5000 Odense C, Denmark. e-mail: henrik.daa.schroeder@rsyd.dk
Summary. Skeletal muscle repair is mediated primarily by the muscle stem cell, the satellite cell. Several factors, including extracellular matrix, are known to regulate satellite cell function and regeneration. One factor, the matricellular Secreted Protein Acidic and Rich in Cysteine (SPARC) is highly up-regulated during skeletal muscle disease, but its function remains elusive.
In the present study, we demonstrate a prominent yet transient increase in SPARC mRNA and protein content during skeletal muscle regeneration that correlates with the expression profile of specific muscle factors like MyoD, Myf5, Myf6, Myogenin, NCAM, CD34, and M-Cadherin, all known to be implicated in satellite cell activation/proliferation following muscle damage. This up regulation was detected in more cell types. Ectopic expression of SPARC in the muscle progenitor cell line C2C12 was performed to mimic the high levels of SPARC seen in muscle disease. SPARC overexpression almost completely abolished myogenic differentiation in these cultures as determined by substantially reduced levels of myogenic factors (Pax7, Myf5, Myod, Mef2a, Myogenin, and Myostatin) and a lack of multinucleated myotubes. These results demonstrate that there is a delicate temporal regulation of SPARC to which more sources in the micro environment contribute, and that disturbances in this, such as extensive up regulation, may have an adverse effect on muscle regeneration. Histol Histopathol 28, 1451-1460 (2013)
Key words: SPARC/osteonectin/BM-40, Skeletal muscle, Myogenic differentiation, Regeneration, Myoblasts
DOI: 10.14670/HH-28.1451