Ascorbic acid diminishes bone morphogenetic protein 2-induced osteogenic differentiation of muscle precursor cells

Muscle precursor cells (MPC) are integral to the maintenance of skeletal muscle and have recently been implicated in playing a role in bone repair. The primary objective of this study was to understand better the role of oxidative stress during the osteogenic differentiation of MPCs.

Muscle precursor cells were treated with various combinations of ascorbic acid (AA), bone morphogenetic protein (BMP)-2, and either a superoxide dismutase analog (4-hydroxy-TEMPO [TEMPOL]) or polyethyleneglycol-conjugated catalase. Muscle precursor cell proliferation and differentiation were determined, and alkaline phosphatase activity was measured as an index of osteogenic differentiation.

After treatment with 200 μM AA, superoxide was increased 1.5-fold, whereas AA in combination with 100 ng/ml BMP-2 did not increase alkaline phosphatase (ALP) activity. When cells were treated with TEMPOL in combination with 100 ng/ml BMP-2 and 200 μM AA, ALP activity significantly increased.

These data suggest that increasing oxidative stress with AA induces sublethal oxidative stress that prevents BMP-2-induced osteogenic differentiation of MPCs. Muscle Nerve 59:501-508, 2019.