Qianqian Di
Kailun Li
Jing Li
Ning Ma
Zhibin Huang
Jiahao Chen
Sheng Zhang
Wenqing Zhang
Yiyue Zhang
aDivision of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, 510006, China
bKey Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases of Guangdong Higher Education Institutes, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China
cDepartment of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
More InformationCorresponding author: E-mail address: mczhangwq@scut.edu.cn (Wenqing Zhang);E-mail address: mczhangyy@scut.edu.cn (Yiyue Zhang)
Publish Date:2020-09-25
Abstract
Abstract
Osteoclasts are bone resorption cells of myeloid origin. Osteoclast defects can lead to osteopetrosis, a genetic disorder characterized by bone sclerosis for which there is no effective drug treatment. It is known that Pu.1 and Fms are key regulators in myelopoiesis, and their defects in mice can lead to reduced osteoclast numbers and consequent osteopetrosis. Yet?how Pu.1 and Fms genetically interact in the development of osteoclasts and the pathogenesis of osteopetrosis is still unclear. Here, we characterized pu.1;fms double-deficient zebrafish, which exhibited a greater deficiency of functional osteoclasts and displayed more severe osteopetrotic symptoms than the pu.1 or fms single mutants, suggesting a synergistic function of Pu.1 and Fms in the regulation of osteoclast development. We further demonstrated that Pu.1 plays a dominant role in osteoclastogenesis, whereas Fms plays a dominant role in osteoclast maturation. Importantly, treatment with the drug retinoic acid significantly relieved the different degrees of osteopetrosis symptoms in these models by increasing the number of functional osteoclasts. Thus, we report the development of valuable animal models of osteopetrosis, and our results shed light on drug development for antiosteopetrosis therapy.Keywords: Zebrafish,
Bone development,
Osteoclasts,
Osteopetrosis,
Therapeutics
PDF全文下载地址:
http://www.jgenetgenomics.org/article/exportPdf?id=1a3b7412-b149-468e-8ed7-ebe47d8b05a2&language=en
