Yukio Akasaki

Reduced expression of FoxO transcription factors in chondrocytes increased susceptibility to cell death induced by oxidative stress. This was associated with reduced levels of antioxidant proteins and autophagy-related proteins. Our data provide evidence for a key role of FoxO transcription factors as regulators of chondrocyte oxidative stress resistance and tissue homeostasis.

The forkhead box O (FOXO) proteins are transcription factors involved in the differentiation of many cell types. <i>Type II collagen</i> (<i>Col2</i>) Cre-<i>Foxo1</i>-knockout and <i>Col2</i>-Cre-<i>Foxo1,3,4</i> triple-knockout mice exhibit growth plate malformation. Moreover, recent studies have reported that in some cells, the expressions and activities of FOXOs are promoted by transforming growth factor β1 (TGFβ1), a growth factor playing a key role in chondrogenic differentiation. Here, us

These findings are the first to suggest that TTR amyloid deposition contributes to cell and extracellular matrix damage in articular cartilage in human OA and that therapies designed to reduce TTR amyloid formation might be useful.

III.

Objective NF ‐κB–dependent signaling is an important modulator in osteoarthritis ( OA ), and G protein–coupled receptor kinase 5 ( GRK 5) regulates the NF ‐κB pathway. This study was undertaken to investigate the functional involvement of GRK 5 in OA pathogenesis. Methods GRK 5 expression in normal and OA human knee joints was analyzed immunohistochemically. Gain‐ or loss‐of‐function experiments were performed using human and mouse chondrocytes. OA was induced in GRK 5‐knockout mice by destabili

This study evaluated the mid-term results of total knee arthroplasty (TKA) following high tibial osteotomy (HTO), comparing posterior cruciate-retaining prostheses to posterior stabilized prostheses. The Knee Society score for the entire group (20 knees) improved significantly from 62 (median) preoperatively to 87 at the latest follow-up. The postoperative Knee Society score of 85 in posterior cruciate-retaining prostheses (8 knees) was significantly inferior to the 94 score in posterior stabili

IV.

These results suggest that IKKε regulates cartilage degradation through a catabolic response mediated by NF-κB signaling, and this could represent a potential target for OA treatment. Furthermore, BAY-985 may serve as a major disease-modifying compound among the drugs developed for OA.

Statins have been shown to have a wide range of anti-inflammatory effects on cells and tissues involved in inflammation that are unrelated to their lipid-lowering abilities. In the progression of osteoarthritis (OA), mediators of inflammation from synovial tissue and cartilage play important roles in initiating or amplifying cartilage degradation in OA. Therefore, we examined the therapeutic efficacy of intra-articularly injected statin in rabbit OA. Intra-articular injections of statin during O