Journal
BIOMATERIALS SCIENCE
Volume 6, Issue 6, Pages 1556-1568Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c8bm00317c
Keywords
-
Categories
Funding
- Key scientific research collaboration program of Guangxi Biomedical Collaborative Innovation Center [GCICB-SR-2017002]
- National key research and development program of China [2016YFB0700804]
- Guangxi Science and Technology Major Project [Guike AA17204085]
- National Natural Science Fund of China [81760326]
- High level innovation teams and outstanding scholars in Guangxi Universities (The third batch)
Ask authors/readers for more resources
Sox9 is a transcription factor that regulates chondrogenesis, but its role in the chondrogenic differentiation of mesenchymal stem cells (MSCs) triggered by materials is poorly understood. In this study, we investigated the effect of Sox9 interference on collagen-induced chondrogenesis and further collagen-based therapies for cartilage defects. In this paper, MSCs were infected with a vector carrying the Sox9 promoter and related markers were detected. A lentivirus-mediated vector targeting the silencing of the Sox9 gene was used in bone marrow-derived MSCs prior to being encapsulated in a collagen hydrogel. The collagen hydrogel as a sole inducer was also compared with transforming growth factor-1 (TGF-1). Before being implanted into the articular cartilage defect in rats, the cell-hydrogel pellets were cultured in vitro for 14 days. The effect of Sox9 transfection on cell proliferation was evaluated by measuring the total DNA content. Safranin-O staining and a biochemistry assay were performed to assess the synthesis and secretion of glycosaminoglycan (GAG) of MSCs. The real-time fluorescent quantitative polymerase chain reaction (RT-PCR) was performed to detect the gene expression levels of Col1a1, Col2a1, Acan and Sox9. The protein expression of collagen type II and collagen type I was analyzed by immunohistochemical analysis. Collagen alone significantly increased the luciferase activity of the Sox9 promoter, which was in parallel with the upregulation of cartilage specific markers. In vitro, the chondrogenic differentiation ability of MSCs was greatly inhibited after Sox9 interference, both in the collagen and TGF-1-induced groups. In vivo, a further study showed that cartilage regeneration was arrested by using transfected MSCs with an injectable collagen gel or induced by TGF-1. The results indicated that collagen may mediate Sox9 expression by providing a biomimetic microenvironment favoring cell condensation prior to chondrogenesis. The role of Sox9 regulation by materials is similar to that by growth factors, suggesting that well-designed scaffolds may replace growth factors in chondrogenesis. Thus, interventions targeting Sox9 may help improve articular cartilage repair.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available