No abstract

We have developed a novel method to induce spontaneous hyaline cartilage regeneration in vivo for a large osteochondral defect by implanting a plug made from a double-network hydrogel composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethylacrylamide) at the bottom of the defect, leaving the cavity vacant. In cells regenerated in the treated defect, type-2 collagen, Aggrican, and SOX9 mRNAs were highly expressed and the regenerated matrix was rich in proteoglycan and type-2 collagen at 4 weeks. This fact gave a significant modification to the commonly established concept that hyaline cartilage tissue cannot regenerate in vivo. This study prompted an innovative strategy in the field of joint surgery to repair an osteochondral defect using an advanced, high-function hydrogel.

Neutral matrix metalloproteinases (MMPs) play an important role in bone matrix degradation accompanied by bone remodeling. We herein show for the first time that macrophage migration inhibitory factor (MIF) upregulates MMP-13 (collagenase-3) mRNA of rat calvariaderived osteoblasts. The mRNA up-regulation was seen at 3 h in response to MIF (10 g/ml), reached the maximum level at 6 -12 h, and returned to the basal level at

Inflammation provokes significant abnormalities in host metabolism that result from the systemic release of cytokines. An early response of the host is hyperglycemia and resistance to the action of insulin, which progresses over time to increased glucose uptake in peripheral tissue. Although the cytokine TNF-␣ has been shown to exert certain catabolic effects, recent studies suggest that the metabolic actions of TNF-␣ occur by the downstream regulation of additional mediators, such as macrophage migration inhibitory factor (MIF). We investigated the glycemic responses of endotoxemic mice genetically deficient in MIF (MIF ؊/؊ ). In contrast to wild-type mice, MIF ؊/؊ mice exhibit normal blood glucose and lactate responses following the administration of endotoxin, or TNF-␣. MIF ؊/؊ mice also show markedly increased glucose uptake into white adipose tissue in vivo in the endotoxemic state. Treatment of adipocytes with MIF, or anti-MIF mAb, modulates insulin-mediated glucose transport and insulin receptor signal transduction; these effects include the phosphorylation of insulin receptor substrate-1, its association with the p85 regulatory subunit of PI3K, and the downstream phosphorylation of Akt. Genetic MIF deficiency also promotes adipogenesis, which is in accord with a downstream role for MIF in the action of TNF-␣. These studies support an important role for MIF in host glucose metabolism during sepsis.

The study evaluated biological reaction of four types of novel double network gels in muscle and subcutaneous tissues, using implantation tests according to the international guideline. The implantation tests demonstrated that, although poly (2-acrylamide-2-metyl-propane sulfonic acid)/poly (N,N'-dimetyl acrylamide) (PAMPS/PDMAAm) gel induced a mild inflammation at 1 week, the degree of the inflammation significantly decreased into the same degree as that of the negative control at 4 and 6 weeks. This gel has a potential to be applied as artificial cartilage. In addition, Cellulose/Gelatin gel showed the same degree of inflammation as that of the negative control at 1 week, and then, showed a gradually absorbable property at 4 and 6 weeks. This gel has a potential to be applied as an absorbable implant. The PAMPS/polyacrylamide and Cellulose/PDMAAm gels induced a significant inflammation at each week. These DN gels are difficult to be applied as clinical implants in the current situation.