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Rmrp Mutation Disrupts Chondrogenesis and Bone Ossification in Zebrafish Model of Cartilage‐Hair Hypoplasia via Enhanced Wnt/β‐Catenin Signaling
Author(s) -
Sun Xianding,
Zhang Ruobin,
Liu Mi,
Chen Hangang,
Chen Liang,
Luo Fengtao,
Zhang Dali,
Huang Junlan,
Li Fangfang,
Ni Zhenhong,
Qi Huabing,
Su Nan,
Jin Min,
Yang Jing,
Tan Qiaoyan,
Du Xiaolan,
Chen Bo,
Huang Haiyang,
Chen Shuai,
Yin Liangjun,
Xu Xiaoling,
Deng Chuxia,
Luo Lingfei,
Xie Yangli,
Chen Lin
Publication year - 2019
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3820
Subject(s) - zebrafish , wnt signaling pathway , endochondral ossification , cartilage , ossification , biology , endocrinology , osteochondrodysplasia , microbiology and biotechnology , medicine , anatomy , gene , genetics , signal transduction
Cartilage‐hair hypoplasia (CHH) is an autosomal recessive metaphyseal chondrodysplasia characterized by bone dysplasia and many other highly variable features. The gene responsible for CHH is the RNA component of the mitochondrial RNA‐processing endoribonuclease ( RMRP ) gene. Currently, the pathogenesis of osteochondrodysplasia and extraskeletal manifestations in CHH patients remains incompletely understood; in addition, there are no viable animal models for CHH. We generated an rmrp KO zebrafish model to study the developmental mechanisms of CHH. We found that rmrp is required for the patterning and shaping of pharyngeal arches. Rmrp mutation inhibits the intramembranous ossification of skull bones and promotes vertebrae ossification. The abnormalities of endochondral bone ossification are variable, depending on the degree of dysregulated chondrogenesis. Moreover, rmrp mutation inhibits cell proliferation and promotes apoptosis through dysregulating the expressions of cell‐cycle‐ and apoptosis‐related genes. We also demonstrate that rmrp mutation upregulates canonical Wnt/β‐catenin signaling; the pharmacological inhibition of Wnt/β‐catenin could partially alleviate the chondrodysplasia and increased vertebrae mineralization in rmrp mutants. Our study, by establishing a novel zebrafish model for CHH, partially reveals the underlying mechanism of CHH, hence deepening our understanding of the role of rmrp in skeleton development.