Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling

Autor: Chengzhi Wu, Hengyu Liu, Dongmei Zhong, Xiaoming Yang, Zhiheng Liao, Yuyu Chen, Shun Zhang, Deying Su, Baolin Zhang, Chuan Li, Liru Tian, Caixia Xu, Peiqiang Su
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Genes and Diseases, Vol 11, Iss 2, Pp 964-977 (2024)
Druh dokumentu: article
ISSN: 2352-3042
DOI: 10.1016/j.gendis.2023.02.012
Popis: 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; Mapk7f/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.
Databáze: Directory of Open Access Journals