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

Bone Development/genetics
Osteogenesis/genetics
Chondrogenesis
STAT3 Transcription Factor*/genetics
Humans
Animals
Zebrafish*/genetics

(all 7)

PubMed

38203559 Full text @ Int. J. Mol. Sci.

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

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