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  • Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis.

Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis.

Aging (2020-08-04)
Marta Varela-Eirín, Paula Carpintero-Fernández, Agustín Sánchez-Temprano, Adrián Varela-Vázquez, Carlos Luis Paíno, Antonio Casado-Díaz, Alfonso Calañas Continente, Virginia Mato, Eduardo Fonseca, Mustapha Kandouz, Alfonso Blanco, José Ramón Caeiro, María D Mayán
ZUSAMMENFASSUNG

Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our in vitro results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
Monoklonaler Anti-α-Tubulin-Antikörper in Maus hergestellte Antikörper, clone DM1A, ascites fluid
Sigma-Aldrich
Fluorescein-di-(β-D-galactopyranosid)
Sigma-Aldrich
Monoclonal Anti-IL6, (C-terminal) antibody produced in mouse, clone 3F4, purified immunoglobulin, buffered aqueous solution

Soziale Medien

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