Back to Search
Start Over
Fibulin-3 regulates the inhibitory effect of TNF-α on chondrocyte differentiation partially via the TGF-β/Smad3 signaling pathway
- Source :
- Biochimica et biophysica acta. Molecular cell research. 1869(9)
- Publication Year :
- 2021
-
Abstract
- Fibulin-3 is an extracellular matrix glycoprotein that is present in elastic tissue and involved in carcinoma development. Previous studies have indicated that fibulin-3 may affect skeletal development, cartilage, and osteoarthritis (OA). This study aims to investigate the function of fibulin-3 on chondrocytes under tumor necrosis factor alpha (TNF-α) stimulation and in murine OA models, and explore the possible mechanism. It was found that fibulin-3 was increased in the cartilage of OA models and in the chondrogenic cells ATDC5 stimulated by TNF-α. Fibulin-3 promoted the proliferation of ATDC5 cells both in the presence and absence of TNF-α. Moreover, overexpression of fibulin-3 suppressed the chondrogenic and hypertrophic differentiation of ATDC5 cells, while knockdown of fibulin-3 caused the opposite effect. Mechanistically, fibulin-3 partially suppressed the activation of TGF-β/Smad3 signaling by inhibiting the phosphorylation of Smad3. SIS3, a Smad3 inhibitor, decreased the chondrogenesis of articular cartilages in OA models, and partially reversed the chondrogenic differentiation of ATDC5 cells caused by knockdown of fibulin-3 in the presence of TNF-α. Furthermore, co-immunoprecipitation (Co-IP) showed that fibulin-3 could only interact with TGF-β type I receptor (TβRI), although overexpression of fibulin-3 reduced the protein levels of both TβRI and TβRII. In conclusion, this study indicates that fibulin-3 modulates the chondrogenic differentiation of ATDC5 cells in inflammation partially via TGF-β/Smad3 signaling pathway.
Details
- ISSN :
- 18792596
- Volume :
- 1869
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta. Molecular cell research
- Accession number :
- edsair.doi.dedup.....fee3a4dd27c6303a986d31e23a478e8f