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Abstract
Objectives: To explore whether Rg3, a major and especially potent ginsenoside, modulates human osteoarthritic (OA) chondrocyte senescence.
Methods: Isolated chondrocytes were cultured in medium containing interleukin-1 beta (IL-1β) with or without Rg3. The expression levels of mRNAs encoding aggrecan (ACAN), a major structural proteoglycan, type II collagen (COL2A1), and metalloproteinases (MMP) -1, -3, and -13, respectively, were determined using real-time PCR. Cellular senescence was detected by measuring senescence-associated β-galactosidase (SA-β-Gal) activity. Chondrocyte telomerase activity also served as a senescence marker.
Results: Chondrocytes stimulated by IL-1β showed increased MMP-1, MMP-3, and MMP-13 levels, whereas the expression of COL2A1 and ACAN decreased. However, in cells co-treated with IL-1β and Rg3, the levels of MMP-1 and MMP-13 were lower than in cells treated with IL-1β alone, and COL2A1 and ACAN expression levels recovered from the low values seen when cultured only in the presence of IL-1β. Also, compared to vehicle-treated controls, IL-1β stimulation alone resulted in an increased number of SA-β-Gal-positive cells, while co-incubation with IL-1β and Rg3 significantly suppressed the expression of this senescence marker. Chondrocytes cultured with Rg3 showed significantly higher proliferative and telomerase activities than did control cells.
Conclusions: These findings indicate that Rg3 protects the cell against the development of chondrocyte senescence in osteoarthritis.