Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling
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Full-length article|更新时间:2024-02-04
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Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling
Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling
Genes & Diseases2024年11卷第2期
作者机构:
1. Department of Orthopedics, Renmin Hospital of Wuhan University,Hubei,Wuhan,China,430060
2. Guangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure Research, School of Basic Medical Sciences, Southern Medical University,Guangdong,Guangzhou,China,510515
3. Precision Medicine Institute, The First Affiliated Hospital of Sun Yat-sen University,Guangdong,Guangzhou,China,510080
4. Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University,Guangdong,Guangzhou,China,510080
5. Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University,Guangdong,Guangzhou,China,510080
Chengzhi Wu, Hengyu Liu, Dongmei Zhong, et al. Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling[J]. Genes & Diseases, 2024,11(2). DOI: 10.1016/j.gendis.2023.02.012.
Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling
摘要
Abstract
Mutation of the MAPK7 gene was related to human scoliosis.
Mapk7
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
Col2a1-cre; Mapk7
f/f
transgenic mouse model to delete
Mapk7
in cartilage
which displayed kyphosis and osteopenia. Mechanistically
Mapk7
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.
In vivo
systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by
Mapk7
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.