BackgroundThe Cadherin-11 and PI3K/Akt pathway are increasingly recognized as the potential therapeutic target of osteoarthritis (OA) synovitis. The study aimed to investigate the role of PI3K/Akt signaling pathway in the expression of Cadherin-11 and migration and invasive capacity of fibroblast-like synoviocytes (FLS) of OA patients under stimulation of TNF-α and to explore the effect of the PI3K/Akt inhibitor and Cadherin-11 antibody in the therapy of the collagenase-induced osteoarthritis (CIOA) mice.MethodsFLS were primarily cultured from synovium of osteoarthritic patients during total knee arthroplasty. Under the simulation of TNF-α, with or without PI3K/Akt inhibitor LY294002, Cadherin-11 expression was detected by real-time PCR and Western blot, as well as the migration and invasive capacity changes of OA FLS. Cadherin-11 antibody was injected intraarticularly or LY294002 was injected intraperitoneally in CIOA mice to evaluate the changes of synovitis score, cartilage damage, and Cadherin-11 expression.ResultsTNF-α stimulation increased Cadherin-11 expression at mRNA and protein level in OA FLS and also increased the phosphorylation-dependent activation of Akt. PI3K inhibitor LY294002 attenuated TNF-α-induced overexpression of Cadherin-11 and decreased the invasive capacity of OA FLS. Intraperitoneal injection of PI3K inhibitor LY294002 could decrease the Cadherin-11 protein expression in synovium of CIOA mice, although it has no significant inhibitory effect on synovitis and cartilage damage. Intraarticular injection of Cadherin-11 antibody attenuated the synovitis and cartilage damage in the CIOA joints and decreased Cadherin-11 expression in the synovial lining.ConclusionsPI3K/Akt pathway was associated with TNF-α-induced activation of OA FLS, which may involve in the pathogenesis of osteoarthritis. Anti-Cadherin-11 therapy in CIOA mice could attenuate the pathological changes of OA joints.

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It has been demonstrated that β‑arrestin2 is involved in the initiation and development of many types of cancers. However, its role in colorectal cancer (CRC) remains poorly understood. The present study investigated the role of β‑arrestin2 in CRC using CRC patient tissues as well as the LoVo and HCT116 CRC cell lines. Briefly, significantly higher expression of β‑arrestin2 was observed in CRC tissues compared with normal colon tissues. In addition, the downregulation of β‑arrestin2 reduced 5‑FU‑induced apoptosis in the LoVo cells, while the overexpression of β‑arrestin2 increased the apoptosis of HCT116 cells in vitro. Furthermore, the downregulation of β‑arrestin2 reduced the expression of the pro‑apoptotic proteins cleaved‑caspase‑3 and Bax, and increased the expression of the anti‑apoptotic protein Bcl‑2 after 5‑FU treatment. In addition, the expression of p‑p65 was increased after the β‑arrestin2 downregulation and was decreased after the β‑arrestin2 overexpression. However, β‑arrestin2 downregulation had no effect on the proliferation, migration and invasion capacity of the LoVo cells. In conclusion, these results indicated that β‑arrestin2 promoted 5‑FU‑induced CRC cell apoptosis via the NF‑κB pathway and may be used as a prognosis marker for CRC.