PUBLICATION
Genetic regulation of injury induced heterotopic ossification in adult zebrafish
- Authors
- Kaliya-Perumal, A.K., Celik, C., Carney, T.J., Harris, M.P., Ingham, P.W.
- ID
- ZDB-PUB-240513-10
- Date
- 2024
- Source
- Disease models & mechanisms 17(5): (Journal)
- Registered Authors
- Carney, Tom, Harris, Matthew, Ingham, Philip
- Keywords
- Contusion, Heterotopic Ossification, Interleukin-11, Myositis Ossificans, Potassium Channels
- MeSH Terms
-
- Aging/genetics
- Aging/pathology
- Animals
- Disease Models, Animal
- Gene Expression Regulation
- Mutation/genetics
- Ossification, Heterotopic*/genetics
- Ossification, Heterotopic*/pathology
- Wounds and Injuries/complications
- Wounds and Injuries/genetics
- Wounds and Injuries/pathology
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 38736327 Full text @ Dis. Model. Mech.
Citation
Kaliya-Perumal, A.K., Celik, C., Carney, T.J., Harris, M.P., Ingham, P.W. (2024) Genetic regulation of injury induced heterotopic ossification in adult zebrafish. Disease models & mechanisms. 17(5):.
Abstract
Heterotopic ossification is the inappropriate formation of bone in soft tissues of the body. It can manifest spontaneously in rare genetic conditions or as a response to injury, known as acquired heterotopic ossification. There are several experimental models for studying acquired heterotopic ossification from different sources of damage. However, their tenuous mechanistic relevance to the human condition, invasive and laborious nature and/or lack of amenability to chemical and genetic screens, limit their utility. To address these limitations, we developed a simple zebrafish injury model that manifests heterotopic ossification with high penetrance in response to clinically-emulating injuries as observed in human myositis ossificans traumatica. Exploiting this model, we defined the transcriptional response to trauma, identifying differentially regulated genes. Mutant analyses revealed that an increase in potassium channel Kcnk5b activity potentiates injury response, while loss of interleukin 11 receptor paralogue (Il11ra) function resulted in a drastically reduced ossification response. Based on these findings, we postulate that enhanced ionic signalling, specifically through Kcnk5b, regulates the intensity of the skeletogenic injury response, which, in part, requires immune response regulated by Il11ra.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping