Wu Chengzhi, Liu Hengyu, Zhong Dongmei, Yang Xiaoming, Liao Zhiheng, Chen Yuyu, Zhang Shun, Su Deying, Zhang Baolin, Li Chuan, Tian Liru, Xu Caixia, Su Peiqiang
Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Precision Medicine Institute, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
Genes Dis. 2023 Mar 24;11(2):964-977. doi: 10.1016/j.gendis.2023.02.012. eCollection 2024 Mar.
Mutation of the MAPK7 gene was related to human scoliosis. regulated the development of limb bones and skulls in mice. However, the role of MAPK7 in vertebral development is still unclear. In this study, we constructed transgenic mouse model to delete in cartilage, which displayed kyphosis and osteopenia. Mechanistically, loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes, which impaired chondrocyte hypertrophy and attenuated vertebral ossification. , systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by deficiency. Our study firstly clarified the mechanism by which MAPK7 was involved in vertebral development, which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.
MAPK7基因的突变与人类脊柱侧弯有关，它在小鼠中调控四肢骨骼和颅骨的发育。然而，MAPK7在脊椎发育中的作用仍不清楚。在本研究中，我们构建了转基因小鼠模型以在软骨中缺失该基因，该模型表现出脊柱后凸和骨质减少。机制上，该基因缺失降低了MEF2C的表达，从而激活PTEN以对抗椎体生长板软骨细胞中的PI3K/AKT信号传导，这损害了软骨细胞肥大并减弱了椎体骨化。此外，AKT的全身药理学激活挽救了受损的软骨细胞肥大，并减轻了由该基因缺陷引起的小鼠椎体缺陷。我们的研究首次阐明了MAPK7参与脊椎发育的机制，这可能有助于理解脊柱畸形的病理学，并为治疗脊柱发育障碍提供依据。
