Berberine ameliorates cartilage degeneration in interleukin‐1β‐stimulated rat chondrocytes and in a rat model of osteoarthritis via Akt signalling

Abstract

Berberine, a plant alkaloid used in Chinese medicine, has broad cell-protective functions in a variety of cell lines. Chondrocyte apoptosis contributes to the pathogenesis of cartilage degeneration in osteoarthritis (OA). However, little is known about the effect and underlying mechanism of berberine on OA chondrocytes. Here, we assessed the effects of berberine on cartilage degeneration in interleukin-1β (IL-1β)-stimulated rat chondrocytes and in a rat model of OA. The results of an MTT assay and western blotting analysis showed that berberine attenuated the inhibitory effect of IL-1β on the cell viability and proliferating cell nuclear antigen expression in rat chondrocytes. Furthermore, berberine activated Akt, which triggered p70S6K/S6 pathway and up-regulated the levels of aggrecan and Col II expression in IL-1β-stimulated rat chondrocytes. In addition, berberine increased the level of proteoglycans in cartilage matrix and the thickness of articular cartilage, with the elevated levels of Col II, p-Akt and p-S6 expression in a rat OA model, as demonstrated by histopathological and immunohistochemistry techniques. The data thus strongly suggest that berberine may ameliorate cartilage degeneration from OA by promoting cell survival and matrix production of chondrocytes, which was partly attributed to the activation of Akt in IL-1β-stimulated articular chondrocytes and in a rat OA model. The resultant chondroprotective effects indicate that berberine merits consideration as a therapeutic agent in OA.

Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling

“…We think the result could be mainly ascribed to the following aspects. First, in this study, definite concentrations of BBR exhibited the anti-apoptotic and chondroprotective effects on OA chondrocytes similar to previous studies [27,28]. Second, the interaction between BBR and SNP could be mutual influence and restriction so as to achieve dynamic balance for treatment.…”

“…Recent studies have demonstrated that BBR decreases IL-1b-stimulated glycosaminoglycan release and NO production, and down-regulates matrix metalloproteinases expression in vitro and in vivo [26,27]. BBR was also shown to protect articular cartilage from degeneration via activating Akt/p70S6K/S6 signaling pathway in IL-1b-induced articular chondrocytes and in a rat OA model [28]. Nevertheless, few data is available on the therapeutic mechanism for BBR on SNP-stimulated chondrocyte apoptosis.…”

Deletion of the PH-domain and Leucine-rich Repeat Protein Phosphatase 1 (Phlpp1) Increases Fibroblast Growth Factor (Fgf) 18 Expression and Promotes Chondrocyte Proliferation

“…Our results show that Phlpp1 is a regulator of endochondral bone development, as chondrocyte proliferation and matrix synthesis are enhanced in Phlpp1-deficient mice. This likely occurs due to the ability of Phlpp1 to directly control the activity of anabolic signaling pathways, including Akt2, PKC, and p70 S6 kinase, that are known facilitators of proliferation and matrix production by chondrocytes (21,37,38). Activation of these pathways triggers subsequent events, including but not limited to, Fgf18 production and downstream activation of Fgfr and Mek/Erk signaling.…”

Lactoferrin Inhibits IL-1β-Induced Chondrocyte Apoptosis Through AKT1-Induced CREB1 Activation

“…Recently, IL-1β has been widely used as a chondrocyte apoptosis-inducing agent. When exposed to IL-1β (10 ng/mL) for 2 h, chondrocyte apoptosis is significantly increased compared to the control group [9,29]. Previously, we showed that LF inhibited Dex-induced OA apoptosis of chondrocytes at a concentration of 200 μg/mL.…”

“…The ginsenoside Rg1 may protect chondrocytes from IL-1β-induced apoptosis via the PI3K/AKT signaling pathway [36]. Berberine ameliorates cartilage degeneration in IL-1β-stimulated rat chondrocytes and in a rat model of OA via AKT signaling [29]. It has been reported that AKT signaling is one crucial upstream signaling pathway for CREB expression [37,38].…”