RT Journal Article
T1 Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis.
A1 Varela-Eirin, Marta
A1 Carpintero-Fernandez, Paula
A1 Sanchez-Temprano, Agustin
A1 Varela-Vazquez, Adrian
A1 Paino, Carlos Luis
A1 Casado-Diaz, Antonio
A1 Calañas-Continente, Alfonso
A1 Mato, Virginia
A1 Fonseca, Eduardo
A1 Kandouz, Mustapha
A1 Blanco, Alfonso
A1 Caeiro, Jose Ramon
A1 Mayan, Maria D
K1 Connexin43
K1 Dedifferentiation
K1 Osteoarthritis
K1 Senescence
K1 Tissue regeneration
AB 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.
PB Impact Journals LLC
YR 2020
FD 2020-07-13
LK http://hdl.handle.net/10668/16037
UL http://hdl.handle.net/10668/16037
LA en
NO Varela-Eirín M, Carpintero-Fernández P, Sánchez-Temprano A, Varela-Vázquez A, Paíno CL, Casado-Díaz A, et al. Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis. Aging (Albany NY). 2020 Aug 3;12(16):15882-15905
DS RISalud
RD Apr 19, 2025