To explore whether Rg3, a major and especially potent ginsenoside, modulates human osteoarthritic (OA) chondrocyte senescence.
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.
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.
These findings indicate that Rg3 protects the cell against the development of chondrocyte senescence in osteoarthritis.