FIGURE 4.

Ferulic acid (FA) partially rescues irradiation‐induced stemness impairment of skeletal stem cells (SSCs) by activating the p38/MAPK and ERK/MAPK pathways. Supplementation with FA (30 μM) significantly restored the phosphorylation of p38/MAPK and ERK/MAPK in irradiated SSCs (A). No obvious effects of FA on the phosphorylated JNK and total JNK proteins in nonirradiated SSCs and irradiated SSCs were observed. Inhibition of p38/MAPK and ERK/MAPK signaling by specific inhibitors (SB203580 and PD98059) abolished the promoting effects of FA on the mRNA expression of Stc1 and Bmpr1b (B). Additionally, the Cell Counting Kit 8 (CCK‐8) assay data demonstrated that SB203580 and PD98059 blocked the rescued effects on cell proliferation in irradiated SSCs (C). Moreover, SB203580 and PD98059 significantly suppressed alkaline phosphatase (ALP) activity, osteogenic mineralization and the mRNA expression of Run2 and OPN in irradiated cells in the presence of FA (D‐F). Furthermore, the colony numbers of irradiated SSCs in the FA‐buffered culture system, and the mRNA expression of Nanog and Sox2 dramatically decreased in the presence of SB203580 and PD98059, respectively (G‐J). Bars in D and G represent 200 and 500 μm, respectively. *P < .05, **P < .01, ***P < .001