Liu Jinan, Wang Jiran, Huang Rui, Jia Xueting, Huang Xiaofeng
Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Department of Stomatology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Immunology Research Center for Oral and Systemic Health, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Tissue Cell. 2025 Feb;92:102643. doi: 10.1016/j.tice.2024.102643. Epub 2024 Nov 28.
Tooth eruption, a critical stage in tooth development, is related to osteoclastogenesis. Intraperitoneal injection of Shh agonists into neonatal mice promoted tooth eruption at postnatal day (PN) 15, whereas treatment with the Shh inhibitor (LDE225) suppressed this process. When RAW264.7 osteoclast precursor cells were treated with RANKL, NFATc1 translocated from the cytoplasm to the nucleus and induced cell differentiation into TRAP osteoclasts; this process was activated by Shh but inhibited by LDE225. Treating RAW264.7 cells with the p38 inhibitor, BIRB796, also inhibited NFATc1 nuclear localization. p-p38 expression in the alveolar bone of PN3 and PN5 mice was decreased by treatment with LDE225, and RAW264.7 cell differentiation was reduced by BIRB796, regardless of treatment with Shh. Furthermore, Shh activated p38 signaling pathway in RAW264.7 cells, while p38 phosphorylation was reduced by LDE225, which ultimately inhibited osteoclast precursor differentiation. Therefore, we concluded that Shh promotes osteoclast precursor differentiation via the p38-NFATc1 signaling pathway.
牙齿萌出是牙齿发育的关键阶段，与破骨细胞生成有关。向新生小鼠腹腔注射Shh激动剂可促进出生后第15天（PN15）的牙齿萌出，而用Shh抑制剂（LDE225）处理则会抑制这一过程。当RAW264.7破骨细胞前体细胞用RANKL处理时，NFATc1从细胞质转移到细胞核并诱导细胞分化为TRAP破骨细胞；这一过程被Shh激活，但被LDE225抑制。用p38抑制剂BIRB796处理RAW264.7细胞也会抑制NFATc1的核定位。用LDE225处理可降低PN3和PN5小鼠牙槽骨中p-p38的表达，无论是否用Shh处理，BIRB796都会降低RAW264.7细胞的分化。此外，Shh激活RAW264.7细胞中的p38信号通路，而LDE225可降低p38磷酸化，最终抑制破骨细胞前体分化。因此，我们得出结论，Shh通过p38-NFATc1信号通路促进破骨细胞前体分化。
