Bone Abstracts

Objectives: Dysregulation of systemic phosphate homeostasis is often associated with impairment of musculoskeletal tissue function. Many factors such as calcium levels and dysegulated endocrine mechanisms are thought to contribute. Inorganic phosphate and FGF23 have been shown to act via similar signaling 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.

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 did not alter gene expression of C2C12 cells or change the effects observed under phosphate treatment.

Conclusion: High phosphate loads directly inhibited muscle cell differentiation 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 hyperphosphatemia and aid to prevent musculoskeletal diseases.

Disclosure: The authors declared no competing interests.