TGF-β3 enhances cell-to-cell communication in chondrocytes via the ALK5/p-Smad3 axis

  • Biochem Biophys Res Commun. 2022 Dec 25;636(Pt 1):64-74. doi: 10.1016/j.bbrc.2022.10.069.
Lang Cai  1 ,  Caixia Pi  1 ,  Daimo Guo  1 ,  Jiazhou Li  1 ,  Hao Chen  1 ,  Demao Zhang  1 ,  Xuedong Zhou  2 ,  Jing Xie  3
Affiliations
  • 1. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 2. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. Electronic address: [email protected].
  • 3. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China; National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China. Electronic address: [email protected].
PMID: 36332484 DOI: 10.1016/j.bbrc.2022.10.069
Abstract

Gap junctional intercellular communication (GJIC) is indispensable for the maintenance of physiological balance in articular cartilage. Transforming growth factor-β3 (TGF-β3), an important growth factor of TGF-β superfamily, is well recognized to play a unique regulatory role in cartilage development and diseases. However, the role of TGF-β3 in GJIC in adult chondrocytes remains elusive. This work aims to investigate the effect of TGF-β3 on gap-junction mediated intercellular communication in chondrocytes. We first showed that TGF-β3 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-β3 enhanced cell-to-cell communication via up-regulation of connexin 43 (Cx43). We next found that TGF-β3-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-β3-induced functional GJIC in chondrocytes via the axis of ALK5/p-Smad3 signalling. Taking together, these results demonstrate a strong correlation between TGF-β3 and GJIC in chondrocytes, which provides a new perspective on the importance of TGF-β3 on cartilage physiology and pathobiology.

Keywords
ALK5; Chondrocyte; Connexin43; Gap junctional intercellular communication; TGF-β3; p-Smad3 signalling.
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