Priority Research Paper Volume 12, Issue 16 pp 15882—15905

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

Figure 7. Cx43 overactivity contributes to disease progression. Cx43 overexpression leads to accumulation of dedifferentiated and senescent cells involved in disease progression in OA patients. These phenotypic changes results in the synthesis of ECM remodeling factors involved in tissue degradation (MMPs) and proinflammatory factors, such as IL-1ß and IL-6, which facilitate the dedifferentiation and reprogramming of neighboring cells. These factors may further spread senescence and dedifferentiation to surrounding tissues contributing to joint degeneration. Downregulation of Cx43 by oleuropein treatment contributes to the elimination of senescent cells and redifferentiation of osteoarthritic chondrocytes into fully differentiated cells, able to support the ECM composition and restoring the regenerative capacity of the tissue. However, oleuropein may have other targets that may contribute to the drug effect. In addition, oleuropein treatment might improve the effectiveness of stem cell therapy, by promoting chondrogenic and osteogenic differentiation, and by inhibiting adipogenesis.