Figure 7.

Modulation of Notch signaling attenuates the proliferation and differentiation defect of Stra13^−/− cells and improves muscle regeneration. (A) WT and Stra13^−/− myoblasts were cultured in growth medium in the absence and presence of Jagged-Fc. Cells were pulsed with BrdU and stained with anti-BrdU antibody. The percentage of BrdU-positive cells was significantly lower in Jagged-Fc–treated Stra13^−/− cells compared with untreated cells. Data are means ± SEM (error bars; n = 4). ^*, P < 0.05. (B) WT and Stra13^−/− myoblasts were cultured in the absence and presence of Jagged-Fc in differentiation medium for 4 d. Myogenic differentiation was visualized by MHC staining. Note that most nuclei are located within MHC⁺ cells in the presence of Jagged-Fc. (C) Stra13^−/− mice were injured and, 7 d later, injected with Jagged-Fc or the control vehicle. 3 d after injection, muscle was analyzed histologically by HE staining. Using ImageJ, the area covered by necrotic fibers within the total damaged area was analyzed for each animal. Mean areas were compared and quantified. Jagged-Fc–injected muscle shows reduced necrosis (arrows) compared with the control uninjected muscle (P < 0.05). (D) Control and Jagged-Fc–injected sections were stained with anti-Ki67 antibody. A reduction in Ki67⁺ cells in the Jagged-Fc–injected muscles was seen by immunostaining. The results are representative of three independent animals.