Loss of ZC4H2, an Arthrogryposis Multiplex Congenita Associated Gene, Promotes Osteoclastogenesis in Mice

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	Loss of ZC4H2, an Arthrogryposis Multiplex Congenita Associated Gene, Promotes Osteoclastogenesis in Mice
	Zhu, L; Zhang, LL; Cha, JM; Li, CC; Mao, BY
	2024
发表期刊	GENES
卷号	15 期号:9
摘要	ZC4H2 encodes a C4H2-type zinc finger protein, mutations of which lead to a spectrum of diseases known as ZC4H2 associated rare disorders (ZARD). In addition to neurological phenotypes, the most typical symptoms of ZARD are multiple joint contractures of varying degrees, accompanied by abnormal development of muscles and bones, and osteoporosis in some cases. The pathogenic mechanisms of such bone related phenotypes, however, remain unclear. Here, we showed that ZC4H2 is expressed in the developing bones in mice. ZC4H2 knockout mice were neonatal-lethal and smaller in size, with reduced calcification of long bones. Upon induced loss of ZC4H2 postnatally, the femoral bones developed an osteoporosis-like phenotype, with reduced bone mineral density, bone-volume fraction, and trabecular bone number. Knockdown of ZC4H2 showed no clear effect on the expression of osteogenic differentiation genes in in vitro models using mesenchymal stem cells. Interestingly, ZC4H2 knockdown significantly enhanced osteoclast differentiation and bone resorption in induced bone marrow-derived macrophages. We further confirmed that the number of osteoclasts in the long bone of ZC4H2 knockout mice was increased, as well as the expression of the serum bone resorption/osteoporosis marker CTX-1. Our study unveils a new role of ZC4H2 in osteoclast differentiation and bone development, providing new clues on the pathology of ZARD.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14523
专题	科研部门_发育生物学（毛炳宇）
推荐引用方式 GB/T 7714	Zhu, L,Zhang, LL,Cha, JM,et al. Loss of ZC4H2, an Arthrogryposis Multiplex Congenita Associated Gene, Promotes Osteoclastogenesis in Mice[J]. GENES,2024,15(9).
APA	Zhu, L,Zhang, LL,Cha, JM,Li, CC,&Mao, BY.(2024).Loss of ZC4H2, an Arthrogryposis Multiplex Congenita Associated Gene, Promotes Osteoclastogenesis in Mice.GENES,15(9).
MLA	Zhu, L,et al."Loss of ZC4H2, an Arthrogryposis Multiplex Congenita Associated Gene, Promotes Osteoclastogenesis in Mice".GENES 15.9(2024).

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