PI3K/Akt inhibitor partly decreases TNF-α-induced activation of fibroblast-like synoviocytes in osteoarthritis.
J Orthop Surg Res
; 14(1): 425, 2019 Dec 11.
Article
en En
| MEDLINE
| ID: mdl-31829201
ABSTRACT
BACKGROUND:
The 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.METHODS:
FLS 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.RESULTS:
TNF-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.CONCLUSIONS:
PI3K/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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Osteoartritis
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Morfolinas
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Cromonas
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Factor de Necrosis Tumoral alfa
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Fosfatidilinositol 3-Quinasas
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Proteínas Proto-Oncogénicas c-akt
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Sinoviocitos
Límite:
Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Orthop Surg Res
Año:
2019
Tipo del documento:
Article