TGF-ß3 enhances cell-to-cell communication in chondrocytes via the ALK5/p-Smad3 axis.
Biochem Biophys Res Commun
; 636(Pt 1): 64-74, 2022 12 25.
Article
em En
| MEDLINE
| ID: mdl-36332484
ABSTRACT
Gap junctional intercellular communication (GJIC) is indispensable for the maintenance of physiological balance in articular cartilage. Transforming growth factor-ß3 (TGF-ß3), an important growth factor of TGF-ß superfamily, is well recognized to play a unique regulatory role in cartilage development and diseases. However, the role of TGF-ß3 in GJIC in adult chondrocytes remains elusive. This work aims to investigate the effect of TGF-ß3 on gap-junction mediated intercellular communication in chondrocytes. We first showed that TGF-ß3 could enhance the synaptic connections between chondrocytes by scanning electron microscopy (SEM) and promote the cell-to-cell communication in living chondrocytes by scrape loading/dye transfer assay. We then confirmed that TGF-ß3 enhanced cell-to-cell communication via up-regulation of connexin 43 (Cx43). We next found that TGF-ß3-enhanced GJIC required the participation of TGF-beta type I receptor ALK5 and depended on the activation of p-Smad3 signalling. Finally, through inhibitor experiments of SB525334 and SIS3, we demonstrated that TGF-ß3-induced functional GJIC in chondrocytes via the axis of ALK5/p-Smad3 signalling. Taking together, these results demonstrate a strong correlation between TGF-ß3 and GJIC in chondrocytes, which provides a new perspective on the importance of TGF-ß3 on cartilage physiology and pathobiology.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cartilagem Articular
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Condrócitos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article