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Background: Although various alterative models of therapy are used for cartilage repair, no definite conclusion has been reached. Glucosamine (GlcN) is widely used as a nutritional supplement. However, the clinical- evidence-based outcome of GlcN administration remains controversial. N-acetyl-D-glucosamine (GlcNAc), a derivative of GlcN, shows chondroprotective activity and mediates the activation of articular chondrocytes. Therefore, we investigated the effect of intra-articular administration of GlcNAc in rabbits' knee joints with experimental full-thickness articular cartilage (FTAC) defects.Methods: Twelve male adult New Zealand white rabbits, providing 24 knees, were used in this study. FTAC defects were created in the high-weight-bearing area of the medial femoral condyles of bilateral knees. All rabbits were randomly allocated to analysis at postsurgical week 4 or postsurgical week 12. In the week 4 group, rabbits' knees (six per group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 3 weeks, beginning 1 week postoperatively. In the week 12 group, the rabbits' knees (six in each group) were intra-articularly injected with normal saline or with GlcNAc twice per week for 4 weeks, beginning 1 week postoperatively. Rabbits were sacrificed at 4 or 12 weeks after surgery for macroscopic, histological and radiological examinations of the knee joints.Results: All rabbits had no systemic or local adverse effects. The saline and GlcNAc groups showed visible differences in healing of the FTAC defect at the end of testing. At week 4, the GlcNAc group had a higher level of collagen type II (COL II) and showed up-regulated production of transforming growth factor (TGF)-β2 and TGF-β3, suggesting the involvement of endogenous growth factors. At week 12, the GlcNAc group displayed formation of hyaline-like cartilage regeneration with mature chondrocytes (SOX9+), robust glycosaminoglycan (GAG) content, and positive COL II content in both the adjacent cartilage and reparative sites. However, the saline group demonstrated mainly fibrocartilage scar tissue, indicating COL I expression. Furthermore, the GlcNAc group had significantly higher bone volume per tissue volume and higher trabecular thickness than the saline group.Conclusions: Intra-articular GlcNAc may promote the repair of experimental FTAC defects in the rabbit knee joint model. [ABSTRACT FROM AUTHOR]

Abstract: It has been shown that ultrasound (US) stimulation accelerates fracture healing in the animal models and in clinical studies. However, the precise molecular events generated by US in chondrocytes have not been clarified well. Here we found that US stimulation transiently increased the surface expression of α2, α5, β1 or β3 but not α3 or α4 integrins in human chondrocytes, as shown by flow cytometric analysis. US stimulation increased prostaglandin E2 formation as well as the protein and mRNA levels of cyclooxygenase-2 (COX-2). At the mechanistic level, anti-integrin β1 and β3 antibodies or β1 and β3 integrin small interference RNA attenuated the US-induced COX-2 expression. Integrin-linked kinase (ILK) inhibitor (KP-392), Akt inhibitor, NF-κB inhibitor (PDTC) or IκB protease inhibitor (TPCK) also inhibited the potentiating action of US. US stimulation promotes kinase activity of ILK, phosphorylation of Akt. In addition, US stimulation also induces IKKα/β phosphorylation, IκBα phosphorylation, IκBα degradation, p65 phosphorylation at Ser276, p65 and p50 translocation from the cytosol to the nucleus, and κB-luciferase activity. The binding of p65 to the NF-κB element, as well as the recruitment of p300 and the enhancement of p50 acetylation on the COX-2 promoter was enhanced by US. Taken together, our results provide evidence that US stimulation increases COX-2 expression in chondrocytes via the integrin/ILK/Akt/NF-κB and p300 signaling pathway. [Copyright &y& Elsevier]

Articular cartilage is the primary structure in joints which is responsible for withstanding compressive loading; however, it is possible that cartilage also experiences localized tensile loading under various loading and boundary conditions. To date, little is known as to whether chondrocyte functions are dependent on the loading variation, especially when loading is switched from compression to tension. The purpose of this study is to examine the metabolism of chondrocytes under both compressive and tensile loadings in vitro. Our results suggest that synthesis of both collagen II and aggrecan is regulated differently by compression and tension at the mRNA level. Tensile loading significantly inhibited the mRNA expression of both collagen II and aggrecan. Since poor content of collagen II and proteoglycan has been considered a detrimental factor in the integrity of cartilage matrix, cartilage degradation and the possible formation of osteoarthritis may be the consequence of loading patterns switching from compression to tension. [ABSTRACT FROM AUTHOR]

Autologous chondrocyte transplantation (ACT) is a promising method to treat chondral and osteochondral defects. This study introduced a modified method for cell culture in ACT. Porcine chondrocytes were cultured for 3 weeks under low hydrostatic pressure at 250 Pa. The results showed that the dry weight of the cartilage-like membrane in the loading group was 3.0 times more than the control group (no loading) ( p ), and cell numbers were significantly increased by 3.1 times ( p ) after a 3-week culture. Compared with the fresh tissue sample, the mRNA expression of collagen II was not statistically different and the mRNA of aggrecan was only slightly decreased by 19%. These data suggest that the hydrostatic pressure at this level significantly increased the cell numbers and biosynthesis of cultured chondrocytes. [ABSTRACT FROM AUTHOR]

Repairing damaged articular cartilage is challenging due to the limited regenerative capacity of hyaline cartilage. In this study, we fabricated a bilayered poly (lactic-co-glycolic acid) (PLGA) scaffold with small (200–300 μm) and large (200–500 μm) pores by salt leaching to stimulate chondrocyte differentiation, cartilage formation, and endochondral ossification. The scaffold surface was treated with tyramine to promote scaffold integration into native tissue. Porcine chondrocytes retained a round shape during differentiation when grown on the small pore size scaffold, and had a fibroblast-like morphology during transdifferentiation in the large pore size scaffold after five days of culture. Tyramine-treated scaffolds with mixed pore sizes seeded with chondrocytes were pressed into three-mm porcine osteochondral defects; tyramine treatment enhanced the adhesion of the small pore size scaffold to osteochondral tissue and increased glycosaminoglycan and collagen type II (Col II) contents, while reducing collagen type X (Col X) production in the cartilage layer. Col X content was higher for scaffolds with a large pore size, which was accompanied by the enhanced generation of subchondral bone. Thus, chondrocytes seeded in tyramine-treated bilayered scaffolds with small and large pores in the upper and lower parts, respectively, can promote osteochondral regeneration and integration for articular cartilage repair. [ABSTRACT FROM AUTHOR]