期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 636, 期 -, 页码 64-74出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.10.069
关键词
Gap junctional intercellular communication; Connexin43; Chondrocyte; ALK5; p-Smad3 signalling
资金
- National Natural Science Foundation of China [81670978, 81870754, 81771047]
- Sichuan Science and Technology Innovation Talent Project [2022JDRC0044]
This study reveals that TGF-03 plays a promoting role in gap-junction mediated intercellular communication in chondrocytes. It enhances cell-to-cell communication by up-regulating Cx43. TGF-03-induced cell-to-cell communication requires the involvement of TGF-beta type I receptor ALK5 and relies on the activation of p-Smad3 signaling. These findings provide a new perspective on the importance of TGF-03 in cartilage physiology and pathobiology.
Gap junctional intercellular communication (GJIC) is indispensable for the maintenance of physiological balance in articular cartilage. Transforming growth factor -03 (TGF-03), an important growth factor of TGF-0 superfamily, is well recognized to play a unique regulatory role in cartilage development and diseases. However, the role of TGF-03 in GJIC in adult chondrocytes remains elusive. This work aims to investigate the effect of TGF-03 on gap-junction mediated intercellular communication in chondrocytes. We first showed that TGF-03 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-03 enhanced cell-to-cell communication via up -regulation of connexin 43 (Cx43). We next found that TGF-03-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-03-induced functional GJIC in chondrocytes via the axis of ALK5/p-Smad3 signalling. Taking together, these results demonstrate a strong correlation between TGF-03 and GJIC in chondrocytes, which provides a new perspective on the importance of TGF-03 on cartilage physiology and pathobiology.(c) 2022 Elsevier Inc. All rights reserved.
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