PUBLICATION
The synergistic role of Pu.1 and Fms in zebrafish osteoclast-reducing osteopetrosis and possible therapeutic strategies
- Authors
- Liu, W., Di, Q., Li, K., Li, J., Ma, N., Huang, Z., Chen, J., Zhang, S., Zhang, W., Zhang, Y.
- ID
- ZDB-PUB-201120-110
- Date
- 2020
- Source
- Journal of genetics and genomics = Yi chuan xue bao 47(9): 535-546 (Journal)
- Registered Authors
- Keywords
- Bone development, Osteoclasts, Osteopetrosis, Therapeutics, Zebrafish
- MeSH Terms
-
- Animals
- Bone Resorption/genetics
- Cell Differentiation/genetics
- Disease Models, Animal
- Hematopoiesis/genetics
- Humans
- Macrophage Colony-Stimulating Factor/genetics*
- Osteoclasts/metabolism
- Osteogenesis/genetics*
- Osteopetrosis/genetics*
- Osteopetrosis/pathology
- Proto-Oncogene Proteins/genetics*
- Receptor, Macrophage Colony-Stimulating Factor/genetics*
- Sclerosis/genetics
- Trans-Activators/genetics*
- Zebrafish/genetics
- PubMed
- 33184003 Full text @ J. Genet. Genomics
Citation
Liu, W., Di, Q., Li, K., Li, J., Ma, N., Huang, Z., Chen, J., Zhang, S., Zhang, W., Zhang, Y. (2020) The synergistic role of Pu.1 and Fms in zebrafish osteoclast-reducing osteopetrosis and possible therapeutic strategies. Journal of genetics and genomics = Yi chuan xue bao. 47(9):535-546.
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.1G242D;fmsj4e1 double-deficient zebrafish, which exhibited a greater deficiency of functional osteoclasts and displayed more severe osteopetrotic symptoms than the pu.1G242D or fmsj4e1 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping