Psoralen promotes the expression of cyclin D1 in chondrocytes via the Wnt/β-catenin signaling pathway

Abstract

Psoralen (PSO), the active ingredient of Fructus Psoraleae (FP) the dried ripe fruit of Psoralea corylifolia L., has been commonly used in traditional Chinese medicine (TCM) for the treatment of osteoarthritis (OA). We found that PSO activates cartilaginous cellular functions of rat chondrocytes in vitro. However, the effect of PSO on chondrocyte proliferation and the precise mechanisms involved remain to be elucidated. We investigated the effects of PSO on chondrocytes isolated from Sprague-Dawley (SD) rats and evaluated involvement of the Wnt/β-catenin signaling pathway. The viability of chondrocytes treated with PSO was increased in a dose- and time-dependent manner, as assessed by MTT assay. We found that the gene expression and protein levels of Wnt-4, Frizzled-2, β-catenin and cyclin D1 in the PSO-treated chondrocytes were significantly upregulated, while the gene expression and protein level of glycogen synthase kinase-3β (GSK-3β) were downregulated, compared with the untreated chondrocytes. By immunofluorescence, we also found that PSO induced β-catenin nuclear translocation. Importantly, the expression of β-catenin and cyclin D1 was partly inhibited by Dickkopf-1 (DKK-1), an inhibitor of the Wnt/β-catenin signaling pathway. Additionally, Col-II expression in chondrocytes was increased after treatment with PSO. Taken together, these results indicate that PSO promotes chondrocyte proliferation by activating the Wnt/β-catenin signaling pathway, and it may play an important role in the treatment of OA.

Psoralen alleviates high glucose-induced HK-2 cell injury by inhibition of Smad 2 signaling via upregulation of microRNA 874

“…However, different signaling pathways were involved when psoralen was used for the treatment of other diseases [36][37][38]. For example, Wenwei Zheng et al reported that psoralen exhibited anti-OA effect by promoting chondrocytes proliferation through activating Wnt/β-catenin signaling pathway [36].…”

Psoralen alleviates high glucose-induced HK-2 cell injury via upregulating miR-874

“…However, different signaling pathways were involved when psoralen was used for the treatment of other diseases [32][33][34]. For example, Wenwei Zheng et al reported that psoralen exhibited anti-OA effect by promoting chondrocytes proliferation through activating Wnt/β-catenin signaling pathway [32]. Additionally, Xiaohong Wang et al demonstrated that psoralen attenuated breast cancer resistance to chemotherapy through PPSR and P53 signaling pathways [33].…”

Cyclin D1 regulates osteoarthritis chondrocyte apoptosis via WNT3/β-catenin signalling

“…Chondrocyte apoptosis was the pathogenic factor of OA. Beier et al [21] revealed that PTHrP and TGF-beta could activate transcription of the Cyclin D1 promoter to protect the cartilage. Zan et al [13] found that silenced Cyclin D1 gene could suppress the proliferation and induces apoptosis of rat chondrocytes in IL-1b-induced OA.…”

“…Results identified that overexpressing Cyclin D1 could prevent the occurrence of OA. Zheng et al [21] revealed that there was a connection between Cyclin D1 and Wnt-b-catenin signalling pathway. Expression of b-catenin and Cyclin D1 in the Wnt/b-catenin signalling pathway is inhibited by DKK-1, a Wnt/b-catenin signalling pathway inhibitor.…”