PUBLICATION
Contribution of Signal Transducer and Activator of Transcription 3 (STAT3) to Bone Development and Repair
- Authors
- Sobah, M.L., Liongue, C., Ward, A.C.
- ID
- ZDB-PUB-240111-21
- Date
- 2023
- Source
- International Journal of Molecular Sciences 25(1): (Journal)
- Registered Authors
- Liongue, Clifford, Ward, Alister C.
- Keywords
- STAT3, bone, macrophages, neutrophils, regeneration
- MeSH Terms
-
- Animals
- Bone Development/genetics
- Chondrogenesis
- Humans
- Osteogenesis/genetics
- STAT3 Transcription Factor*/genetics
- Zebrafish*/genetics
- PubMed
- 38203559 Full text @ Int. J. Mol. Sci.
Citation
Sobah, M.L., Liongue, C., Ward, A.C. (2023) Contribution of Signal Transducer and Activator of Transcription 3 (STAT3) to Bone Development and Repair. International Journal of Molecular Sciences. 25(1):.
Abstract
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor activated canonically by numerous cytokines and other factors, with significant roles in immunity, immune diseases, and cancer. It has also been implicated in several human skeletal disorders, with loss-of-function (LOF) mutations associated with aberrant skeletal development. To gain further insights, two zebrafish STAT3 lines were investigated: a complete LOF knockout (KO) mutant and a partial LOF mutant with the transactivation domain truncated (ΔTAD). Consistent with other studies, the KO mutants were smaller, with reduced length in early embryos exacerbated by a decreased growth rate from 5 days postfertilization (dpf). They displayed skeletal deformities that approached 80% incidence by 30 dpf, with a significant reduction in early bone but not cartilage formation. Further analysis additionally identified considerable abrogation of caudal fin regeneration, concomitant with a paucity of infiltrating macrophages and neutrophils, which may be responsible for this. Most of these phenotypes were also observed in the ΔTAD mutants, indicating that loss of canonical STAT3 signaling was the likely cause. However, the impacts on early bone formation and regeneration were muted in the ΔTAD mutant, suggesting the potential involvement of noncanonical functions in these processes.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping