The role of the allantoin in promoting fracture healing in osteoclast-deficient zebrafish
Received date: 2023-01-18
Revised date: 2023-02-27
Online published: 2023-03-22
Supported by
National Key Research and Development Program of China(2018YFA0801000);National Natural Science Foundation of China(81770167)
Fracture healing is a rigorous and orderly process with multiple steps that are mediated by multiple cells. During this process, osteoclast-mediated bone remodeling plays a critical role, and its abnormal activity leads not only to fracture susceptibility but also to impaired fracture healing. However, few studies have focused on impaired healing caused by osteoclast defects, and clinical drugs for this type of impaired fracture healing are still lacking. The cell types and regulatory pathways in the zebrafish skeletal system are highly similar to those of mammals, making the zebrafish skeletal system being widely used for skeletal-related studies. To study the process of fracture healing disorders caused by osteoclast defects and discover potential therapeutic drugs, we established an in vivo osteoclast-deficient fracture model using a previously generated fms gene mutant zebrafish (fmsj4e1). The results showed that reduced functional osteoclasts could affect fracture repair in the early stages of fracture. Then we applied an in vitro scale culture system to screen for osteoclast-activating drugs. We found the small molecule compound allantoin (ALL) being able to activate osteoclasts. Subsequently, we verified the activation role of ALL on osteoclasts and the promotion of fracture repair in an in vivo fmsj4e1 fracture defect model. Finally, by examining the osteoclastogenesis and maturation process, we found that ALL may promote osteoclast maturation by regulating RANKL/OPG, thus promoting fmsj4e1 fracture healing. Our study provides a potential new approach for the future improvement of fracture healing disorders caused by osteoclast defects.
Key words： zebrafish fmsj4e1 mutant; osteoclasts; drug screening; allantoin; fracture healing
Kailun Li, Jingao Lu, Xiaohui Chen, Wenqing Zhang, Wei Liu . The role of the allantoin in promoting fracture healing in osteoclast-deficient zebrafish[J]. Hereditas(Beijing), 2023 , 45(4) : 341 -353 . DOI: 10.16288/j.yczz.23-015
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