ESPE Abstracts (2015) 84 P-1-21

Effects of Inorganic Phosphate and FGF23 on C2C12 Myoblast Cells

Adalbert Raimanna, Alexander Dangla, Susanne Greber-Platzera, Monika Egerbacherb & Gabriele Haeuslera

aMedical University Vienna, Vienna, Austria; bUniversity of Veterinary Medicine, Vienna, Austria

Background: Dysregulation of phosphate homeostasis in diseases such as tumor-induced osteomalacia and chronic kidney disease are often associated with impairment of musculoskeletal tissue function. While various factors such as intracellular calcium levels and dysegulated endocrine mechanisms are thought to contribute, the role of single factors such as phosphate and its main regulating hormone FGF23 are only partly revealed.

Objective and hypotheses: Inorganic phosphate and FGF23 have been shown to act via similar signalling pathways in several cell types but we are not aware of any detailed investigations into their effect on the differentiation and viability of skeletal muscle cells. We therefore investigated their effect on skeletal muscle cells in a murine in vitro model.

Method: Murine C2C12 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 analysed by RT-PCR and Immunohistochemistry. Proliferation rate was analysed 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 did not alter gene expression of C2C12 cells or change the effects observed under phosphate treatment.

Conclusion: High phosphate loads inhibited muscle cell differentiation dose-dependently in a C2C12 model system. FGF23/Klotho treatments did not influence these effects. Knowledge of the distinct effects of phosphate could help us to optimize treatment of hyperphosphataemia and ultimately to prevent musculoskeletal diseases.

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