[Retracted] Protective effects of baicalin on rabbit articular chondrocytes in vitro.

[This retracts the article DOI: 10.3892/etm.2017.4116.].

Retraction: The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs).

Retraction of 'The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs)' by Xianfang Jiang et al., Biomater. Sci., 2018, 6, 1556-1568, https://doi.org/10.1039/C8BM00317C.

Erratum: Protective effects of baicalin on rabbit articular chondrocytes in vitro.

[This corrects the article DOI: 10.3892/etm.2017.4116.].

Correction: The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs).

Correction for 'The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs)' by Xianfang Jiang, et al., Biomater. Sci., 2018, 6, 1556-1568.

Impact of Hydrogel Elasticity and Adherence on Osteosarcoma Cells and Osteoblasts.

Biochemical and physical properties of extracellular matrix (ECM) control cell behaviors, but how they affect osteosarcoma cells that do not require attachment and their normal counterparts (osteoblasts) that are anchorage-dependent has not been reported yet. In this study, the effects of matrix elasticity and adherence on osteosarcoma MG63 cells are investigated using four types of scaffolds (collagen type I, matrigel, alginate, and agarose) with varied adhesion ligands and rigidity, as compared with osteoblast hFOB1.19 cells. MG63 cells on 2D films are sensitive to ECM adherence, similar to the situation of hFOB1.19 cultured in both 2D and 3D. However, osteosarcoma cells in 3D hydrogels are sensitive to ECM elasticity rather than adherence, with tumor proliferation and malignancy varied with matrix rigidity. The results indicate that osteosarcomas cells might adopt unnatural characteristics on flat surfaces. But in 3D culture, they recover their normal state independent of adherence, as regulated mainly by ECM elasticity via the integrin-mediated focal adhesion pathway, which is further confirmed by in vivo studies. In contrast, osteoblasts and 2D cultured osteosarcoma cells are predominantly influenced by ECM bioactivity regulated by integrin-mediated adherens junction pathway. This study might provide new insights into rational design of scaffolds for tumor/tissue engineering.

Biomimetic Poly(Poly(ε-caprolactone)-Polytetrahydrofuran urethane) Based Nanofibers Enhanced Chondrogenic Differentiation and Cartilage Regeneration.

Scaffolds for stem cell-based therapy of cartilage defect require bioactivity and stiffness mimicking to the native cartilage matrix. In this study, we fabricated electrospun nanofibers composited of cartilage matrix components (collagen or chondroitin sulfate) and poly(ε-caprolactone)-polytetrahydrofuran (PCL-PTHF). PCL-PTHF with rat tail derived collagen was named PR and PCL-PTHF with chondroitin sulfate (PS) termed PS, which have a modulus of 7.5 MPa and 3.6 MPa, respectively, within the range of cartilage matrix. Their chondrogenic potential for guiding chondrogenic differentiation and promoting cartilage regeneration were investigated based upon mesenchymal stem cells (MSCs). Results showed that both PR and PS nanofibers have the ability to induce chondrogenesis of MSCs and accelerate the regeneration of injured cartilage surface, probably via the suppression of Tumor necrosis factor (TNF) signaling pathway as evidenced by microarray profiles. Comparatively, PR showed better chondrogenic potential both in vitro and in vivo than that of PS, which may induce chondrogenesis through Hypoxia inducing factor-1 (HIF-1) signaling pathway. This study may provide reference for MSC based therapy of cartilage defects.

Mechanically cartilage-mimicking poly(PCL-PTHF urethane)/collagen nanofibers induce chondrogenesis by blocking NF-kappa B signaling pathway.

Cartilage cannot self-repair and thus regeneration is a promising approach to its repair. Here we developed new electrospun nanofibers, made of poly (ε-caprolactone)/polytetrahydrofuran (PCL-PTHF urethane) and collagen I from calf skin (termed PC), to trigger the chondrogenic differentiation of mesenchymal stem cells (MSCs) and the cartilage regeneration in vivo. We found that the PC nanofibers had a modulus (4.3 Mpa) lower than the PCL-PTHF urethane nanofibers without collagen I from calf skin (termed P) (6.8 Mpa) although both values are within the range of the modulus of natural cartilage (1-10 MPa). Both P and PC nanofibers did not show obvious difference in the morphology and size. Surprisingly, in the absence of the additional chondrogenesis inducers, the softer PC nanofibers could induce the chondrogenic differentiation in vitro and cartilage regeneration in vivo more efficiently than the stiffer P nanofibers. Using mRNA-sequence analysis, we found that the PC nanofibers outperformed P nanofibers in inducing chondrogenesis by specifically blocking the NF-kappa B signaling pathway to suppress inflammation. Our work shows that the PC nanofibers can serve as building blocks of new scaffolds for cartilage regeneration and provides new insights on the effect of the mechanical properties of the nanofibers on the cartilage regeneration.

The role of Sox9 in collagen hydrogel-mediated chondrogenic differentiation of adult mesenchymal stem cells (MSCs).

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-ß1 (TGF-ß1). 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-ß1-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-ß1. 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.

Protective effects of baicalin on rabbit articular chondrocytes in vitro.

Drug therapy is one of the typical treatments for post-injury inflammation of cartilage. Traditional Chinese herbs have potential as treatments, as their long history of clinical application has demonstrated they are effective and induce minimal side effects. Baicalin is a traditional Chinese medicine that has been used to treat inflammation, fever, ulcers and cancer for hundreds of years. Previous studies have demonstrated that baicalin may decrease levels of interleukin-1ß and suppress the expression of type-I collagen, thus attenuating cartilage degeneration. In the present study, the effect of baicalin on chondrocytes was assessed by examining the morphology, proliferation, extracellular matrix (ECM) synthesis and cartilage-specific gene expression of chondrocytes. The results indicated that baicalin may promote the proliferation of articular chondrocytes, secretion of cartilage ECM and collagen type II, aggrecan and SRY box (Sox) 9 gene upregulation. The expression of collagen I, a marker of chondrocyte dedifferentiation, was downregulated by baicalin; therefore, baicalin may maintain the phenotype of chondrocytes. Within the recommended concentrations of baicalin ranging from 0.625-6.25 µmol/l cell proliferation was increased and a 1.25 µmol/l dose of baicalin exerted the most positive effect on articular chondrocytes. The results of the present study may therefore indicate that baicalin may be used as a novel agent promoting the repair of articular cartilage damage.