ECTS2016 Poster Presentations Muscle, physical activity and bone (14 abstracts)
Effects of inorganic phosphate and FGF23 on C2C12 myoblast cells
Adalbert Raimann 1 , Alexander Dangl 1 , Alireza Javanmardi 1 , Alexandra Ertl 1 , Monika Egerbacher 2 , Susanne Greber-Platzer 1 & Gabriele Haeusler 1
1Medical University of Vienna, Vienna, Austria; 2University of Veterinary Medicine, Vienna, Austria.
Background: Disturbance of systemic phosphate homeostasis is often associated with musculoskeletal dysfunction. Multiple factors related to the underlying condition such as calcium levels and endocrine mechanisms are thought to contribute. Distinct effects of inorganic phosphate itself as well as its main regulator FGF23 by activation of similar pathways have been shown in several cell types. We are not aware of any detailed investigations into their effect on the differentiation and viability of skeletal muscle cells. Therefore, we investigated their effect on skeletal muscle cells in a murine in vitro model.
Methods: C2C12 muscle progenitor cells were differentiated under single and combined treatments with inorganic phosphate and/or FGF23 and Klotho. Expression of differentiation markers (myogenin, MyHC, MyoD, Myf5) were analyzed by RT-PCR. Proliferation rate was analyzed by measurement of BrdU incorporation. Metabolic activity was examined by EZ4U assays.
Results: Phosphate treatments inhibited the expression of differentiation markers in C2C12 cells in a dose-dependent manner. The altered expression profile was associated with increased proliferation rates and metabolic activity. FGF23/ Klotho treatments partly mimicked gene expression changes under phosphate treatment but did not alter proliferation rates.
Conclusion: High phosphate loads directly inhibited muscle cell differentiation in a C2C12 model system. FGF23/Klotho treatments partly showed similar effects. Knowledge of the distinct effects of phosphate could help us to optimize treatment of hyperphosphatemia and aid to prevent musculoskeletal diseases.
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