Bite Opening Activates PGC-1 Transcription Through Calcineurin-Signaling in Rat Masseter

Objectives: We have previously observed that in rat masseter the mechanical overloading via bite-opening (BO) treatment induces a fast-to-slow transition of myosin heavy chain (MHC), particularly from MHC IIa to I through the calcineurin (CaN)-signaling pathways. Recently, a transcriptional co-activator, peroxisome proliferator-activated receptor g coactivator 1 (PGC-1), has been reported to serve as a target for CaN signaling and activate genes involved in mitochondrial biogenesis and oxidative metabolism in skeletal muscle. To study the effects of bite-opening treatment on intracellular signaling pathways implicated in controlling genes that participate in energy metabolism in rat masseter, we measured PGC-1 mRNA level in BO and/or cyclosporin A (CsA, a CaN inhibitor)-treated rat masseter. Methods: Male Wistar rats, aged 8 weeks, were divided into four groups: (1) control group (n=6), (2) BO-treated group (3 mm increase in the vertical dimension, n=6), (3) CsA-treated group (injected i.p. with 10 mg/kg CsA once daily, n=6) and (4) BO+CsA-treated group (n=6). After 2 weeks of each treatment, we measured PGC-1 mRNA level in rat masseter by using real-time RT-PCR. Results: As compared with control value, PGC-1 mRNA level significantly (p<0.01) increased with the BO treatment, but significantly (p<0.01) decreased with the CsA treatment. PGC-1 mRNA level did not change with the BO+CsA treatment, showing that the BO-induced increase in PGC-1 mRNA level was blocked by the CsA treatment. Conclusions: These results suggest that in rat masseter the BO treatment promotes the up-regulation of PGC-1 transcription through the CaN-signaling pathways to meet altered functional demands, implying a existence of highly coordinated adaptation between contractile proteins and metabolic enzymes.