Participation of GATA-3 in regulation of bone healing through transcriptional upregulation of bcl-x(L) expression.
- Author:
Mei Hsiu LIAO
1
;
Pei I LIN
;
Wei Pin HO
;
Wing P CHAN
;
Ta Liang CHEN
;
Ruei Ming CHEN
Author Information
- Publication Type:Original Article
- MeSH: Alkaline Phosphatase; Animals; Bone Diseases; Cell Survival; Chromatin Immunoprecipitation; Computational Biology; Femur; Fracture Healing; Fractures, Bone; Gene Expression; Humans; Immunoprecipitation; Male; Mice; Mice, Inbred ICR; Microscopy, Confocal; Osteoblasts; Promoter Regions, Genetic; RNA, Messenger; Transcription Factors; Transcriptional Activation; Up-Regulation*; Wounds and Injuries
- From:Experimental & Molecular Medicine 2017;49(11):e398-
- CountryRepublic of Korea
- Language:English
- Abstract: We have previously demonstrated the expression of GATA-DNA-binding protein (GATA)-3, a transcription factor, in osteoblasts and have verified its function in transducing cell survival signaling. This translational study was further designed to evaluate the roles of GATA-3 in regulating bone healing and to explore its possible mechanisms. A metaphyseal bone defect was created in the left femurs of male ICR mice. Analysis by micro-computed topography showed that the bone volume, trabecular bone number and trabecular thickness were augmented and that the trabecular pattern factor decreased. Interestingly, immunohistological analyses showed specific expression of GATA-3 in the defect area. In addition, colocalized expression of GATA-3 and alkaline phosphatase was observed at the wound site. As the fracture healed, the amounts of phosphorylated and non-phosphorylated GATA-3 concurrently increased. Separately, GATA-3 mRNA was induced during bone healing, and, levels of Runx2 mRNA and protein were also increased. The results of confocal microscopy and co-immunoprecipitation showed an association between nuclear GATA-3 and Runx2 in the area of insult. In parallel with fracture healing, Bcl-XL mRNA was significantly triggered. A bioinformatic search revealed the existence of a GATA-3-specific DNA-binding element in the promoter region of the bcl-x(L) gene. Analysis by chromatin immunoprecipitation assays further demonstrated transactivation activity by which GATA-3 regulated bcl-x(L) gene expression. Therefore, this study shows that GATA-3 participates in the healing of bone fractures via regulating bcl-xL gene expression, owing to its association with Runx2. In the clinic, GATA-3 may be used as a biomarker for diagnoses/prognoses or as a therapeutic target for bone diseases, such as bone fractures.
