TGF-ß2 increases cell-cell communication in chondrocytes via p-Smad3 signalling.
Biochim Biophys Acta Mol Cell Res
; 1869(2): 119175, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34863793
ABSTRACT
Connexin 43 (Cx43)-mediated gap junction intercellular communication (GJIC) plays a crucial role in the pathology and physiology of joint tissues. Transforming growth factor-ß2 (TGF-ß2), one of the potent regulatory factors in chondrocytes, plays a key role in the regulation of cell cycle and development of joint diseases. However, it is still unknown how TGF-ß2 mediates GJIC in chondrocytes. The aim of this study was to explore the potential mechanism by which TGF-ß2 regulates GJIC in chondrocytes. CCK-8 assays and scratch assays were performed to define the role of TGF-ß2 on cell proliferation and migration. The scrape loading/dye transfer assay and scanning electron microscopy (SEM) were used to verify the effect of TGF-ß2 on GJIC between chondrocytes. qPCR was performed to analyse the expression of genes in the gap junction protein family in chondrocytes. The expression of the Cx43 protein and phosphorylated Smad3 (p-Smad3) was evaluated by western blot assay. Immunofluorescence staining was used to explore p-Smad3 signalling pathway activation and Cx43 distribution. From these experiments, we found that the Cx43 protein was the most highly expressed member of the gap junction protein family in chondrocytes. We also found that TGF-ß2 facilitated cell-to-cell communication in chondrocytes by upregulating Cx43 expression in chondrocytes. Finally, we found that TGF-ß2 activated Smad3 signalling and promoted the nuclear aggregation of p-Smad3. Inhibition experiments by SIS3 also confirmed that TGF-ß2-mediated GJIC through p-Smad3 signalling. For the first time, this study confirmed that TGF-ß2 could regulate the formation of Cx43-mediated GJIC in chondrocytes via the canonical p-Smad3 signalling pathway.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Comunicação Celular
/
Junções Comunicantes
/
Conexina 43
/
Condrócitos
/
Proteína Smad3
/
Fator de Crescimento Transformador beta2
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article