Zhu Jiayong, Zhao Xiaoqi, Wang Hui, Xiao Hao, Chen Liaobin
Division of Joint Surgery and Sports Medicine, Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China.
Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan, China.
Front Pharmacol. 2023 Mar 2;14:1120041. doi: 10.3389/fphar.2023.1120041. eCollection 2023.
Maternal exposure to dexamethasone can cause developmental toxicity of long bones in offspring. However, the effect of dexamethasone on the trans-differentiation of growth plate chondrocytes into osteoblasts and its role in bone dysplasia of fetuses caused by prenatal dexamethasone exposure (PDE) remains unclear. In this study, pregnant mice were treated with different doses, stages, and courses of dexamethasone according to clinical practice to reveal the phenomenon. Further, growth plate chondrocytes were treated with dexamethasone to clarify the phenomenon and mechanism. The results showed that PDE caused dysplasia of fetal long bones in female and male mice, accompanied by the delayed formation of the primary ossification center and the widening hypertrophic zone of growth plate cartilage. Meanwhile, PDE increased the number of hypertrophic chondrocytes at growth plate cartilage and decreased the number of osteoblasts at the primary ossification center. Moreover, PDE significantly decreased the expression of osteogenic transcription factor Runx2 but increased the expression of hypertrophic chondrocytes marker Col10. These above phenomena were more significant in the high dose, early stage, and double courses of dexamethasone exposure groups, and the male fetal mice showed more obvious than the female fetal mice. , dexamethasone significantly inhibited the trans-differentiation of growth plate chondrocytes into osteoblasts, accompanied by a decrease in Runx2 expression and an increase in Col10 expression. In conclusion, this study revealed the phenomenon and mechanism of fetal bone dysplasia caused by PDE from the new perspective of trans-differentiation disorder of growth plate chondrocytes to osteoblasts.
母体接触地塞米松可导致子代长骨发育毒性。然而，地塞米松对生长板软骨细胞向成骨细胞转分化的影响及其在产前地塞米松暴露（PDE）所致胎儿骨发育异常中的作用尚不清楚。本研究根据临床实际情况，对孕鼠给予不同剂量、阶段和疗程的地塞米松进行处理以揭示该现象。此外，用地塞米松处理生长板软骨细胞以阐明该现象及机制。结果显示，PDE导致雌性和雄性小鼠胎儿长骨发育异常，伴有初级骨化中心形成延迟和生长板软骨肥大带增宽。同时，PDE增加了生长板软骨肥大软骨细胞数量，减少了初级骨化中心成骨细胞数量。此外，PDE显著降低了成骨转录因子Runx2的表达，但增加了肥大软骨细胞标志物Col10的表达。上述现象在高剂量、早期和双疗程地塞米松暴露组中更为显著，且雄性胎儿小鼠比雌性胎儿小鼠表现更明显。地塞米松显著抑制生长板软骨细胞向成骨细胞的转分化，伴有Runx2表达降低和Col10表达增加。总之，本研究从生长板软骨细胞向成骨细胞转分化紊乱的新视角揭示了PDE所致胎儿骨发育异常的现象及机制。
