TABLE 5.
Pharmacological inhibitors of the Wnt/β-catenin signaling pathway.
| Author | Subjects | Inhibitor | Path involved | Results |
|---|---|---|---|---|
| Zhong Gang et al. (2018) | Human OA chondrocytes and rats OA model | Artemisinin | Wnt5a/β-catenin | ART inhibits OA progression and cartilage degradation by exhibiting potent anti-inflammatory effects via the Wnt/β-catenin signaling pathway |
| L Enochson et al. (2014) | Human OA chondrocytes | Growth differentiation factor 5 (GDF5) | Wnt/β-catenin | GDF5 inhibits expression of MMP-13 and ADAMTS-4 and stimulates the expression of cartilage anabolic genes ACAN and SOX9 via the DKK1-mediated Wnt signaling pathway |
| Long Ma et al. (2019) | C57BL/6 mice | Rapamycin | Wnt/β-catenin | Rapamycin injection could activate chondrocyte autophagy, increase the expression of LC3 and ATG-5, reduce OARSI scores, expression of β-catenin, MMP-13, and chondrocyte apoptosis |
| Li Zeng et al. (2014) | Human SW 1353 cells and rats OA model | Icariin | Wnt/β-catenin | Icariin could decrease the MMP-13 expression and reduce the number of cartilage lesions via the Wnt/catenin pathway |
| Yun-Peng Zhao et al. (2014) | C57/BL6 mice and chondrocytes | Progranulin | Wnt/β-catenin | Progranulin suppresses inflammatory action of TNF-α and inhibits the activation of β-catenin signaling in chondrocytes, protects cartilage degradation in spontaneous and surgically induced OA models |
| Caressa Lietman et al. (2018) | Human chondrocytes and C57BL/6 J mice with DMM method of OA model | XAV939 | XAV939 | XAV-939 ameliorates OA severity associated with reduced cartilage degeneration and synovitis |
| Jingyuan Li et al. (2019) | Sprague–Dawley rats and ATDC5 cells | Xanthan gum | Wnt3a/β-catenin | Xanthan Gum reduces the OARSI score and the concentration of inflammatory cytokines in OA. Xanthan Gum acted on Wnt3a/β-catenin in ATDC5 cells to decrease the expression of MMP-13 and ADAMTS-5 |
| Yuzhe He et al. (2019) | Rat chondrocytes and an OA rat model | Costunolide | Wnt/β-catenin | Costunolide decreases IL-1β-induced upregulation of MMPs, INOS, COX-2 and IL-6, increases the expression of Clo2a1 and Sox9 through inhibiting Wnt/β-catenin signaling pathway |
| Fuen Liu et al. (2020) | C57BL/6 mice and human chondrocytes derived from patients | Scutellarin | Wnt3a/β-catenin and MAPK signaling pathway | Scutellarin downregulates the mRNA and protein expression of MMP-1, MMP-13, and ADAMTS-5 and promotes the expression of Col2a1 and aggrecan. Moreover, scutellarin inhibits the migration of β-catenin and phosphorylation of p38 into the nucleus |
| J.-B. Gao et al. (2020) | Human chondrocytes and human knee OA cartilage tissue | Fibulin-5 | Wnt/β-catenin | Fibulin-5 increases the expressions of Col2a1 and aggrecan and reduces IL-1β-induced inflammation of chondrocytes, as well as expressions of IL-6, IL-8, and TNF-αvia reducing the activity of Wnt/β-catenin signaling pathway |
| Qian-Hai Ding et al. (2018) | Rat articular cartilage and chondrocytes | Emodin | NF-κB and Wnt/β-catenin signaling | Emodin dose-dependently down-regulates the expression of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 at both the mRNA and protein level in IL-1β-stimulated rat chondrocytes. In addition, the IL-1β-induces activation of NF-κB and Wnt signals was attenuated by emodin |
| Shan Cong et al. (2021) | Sprague–Dawley (SD) rats | Iguratimod | β-Catenin | Iguratimod improves the degeneration of articular cartilage and decreases the levels of MMP-13, TNF-α, and IL-6 in serum. Iguratimod downregulates the mRNA and protein expression of β-catenin in vivo |
| Xindie Zhou et al. (2016) | New Zealand rabbits and chondrocytes | Palmatine | Wnt/β-catenin and Hedgehog signaling pathways | Palmatine decreases the expression of the MMPs and increases the synthesis of TIMP-1, whereas collagenase II and aggrecan are inhibited by IL-1β. Palmatine protects the cartilage degradation via suppressing the Wnt and hedgehog signaling pathways |
| Yang Xi et al. (2020) | Sprague–Dawley rats and chondrocytes | Erdosteine | MAPK, NF-κB, and Wnt/β-catenin signaling pathways | Erdosteine suppresses the expressions of IL-1β-induced production of inflammatory factors COX-2 and iNOS and attenuates the degradation of ECM by repressing the expression of MMP-1, MMP-3, and MMP-13. Moreover, erdosteine could inhibit the activation of IL-1β-induced MAPK and Wnt/β-catenin |
| Yi-Yue Chen et al. (2019) | Human OA, normal articular cartilage samples, and chondrocytes | Cyclin D1 | Wnt3/β-catenin | Cyclin D1 inhibits cell apoptosis and cell cycle promotes the proliferation OA chondrocytes through activating the Wnt/β-catenin signaling pathway |
| Tangbo Yuan et al. (2022) | 107 OA patients | Curcumin | Wnt/β-catenin | Curcumin can effectively decrease the pathological results of OA, with a remarkable safety profile; its mechanism may be the activation of the Wnt/β-catenin signaling pathway to inhibit the inflammatory reaction and apoptosis in chondrocytes |
| Long Ma et al. (2021) | Female C57BL/6 J OA model mice with ACLT + DHA method | Dihydroartemisinin | Wnt/β-catenin | Dihydroartemisinin decreases MMP-13 and VEGF expression in the articular cartilage, and finally results in decreasing OARSI scores and reducing articular cartilage degeneration. In addition, dihydroartemisinin reduces abnormal subchondral bone remodeling via the Wnt/catenin |
| Xindie Zhou et al. (2013) | New Zealand rabbits and chondrocytes | Tetrandrine | Wnt/β-catenin | Tetrandrine decreases the expression of MMP-1, MMP-3, MMP-13, TIMP-1, and β-catenin in rabbit chondrocytes and cartilage |
| De-Heng Chen et al. (2021) | Human chondrocyte and C57BL/6 J OA model | Oroxylin A | NF-κB and Wnt/β-catenin signaling | Oroxylin A could rescue IL-1β-mediated hypertrophic alterations of chondrocytes and inhibit the ECM hemostasis in human chondrocytes. Oroxylin A attenuates the IL-1β-induced hypertrophic changes in chondrocytes by inhibiting the Wnt/β-catenin signaling pathway |
| Nan Yao et al. (2021) | Sprague–Dawley rats | Bushen Qiangjin capsule | Wnt/β-catenin | Bushen Qiangjin capsule obviously reduces pathological damage and matrix degradation of articular cartilage in KOA rats and downregulates mRNA and protein expression of Wnt-4, β-catenin, Frizzled-2, and caspase-3 |
| Wei-Ping Chen et al. (2017) | Rat chondrocytes | Licochalcone A | NF-κB and Wnt/β-catenin signaling pathways | Licochalcone A inhibits ADAMTS-5, ADAMTS-4, MMP-13, and MMP-1 expression via inhibiting the NF-κB and Wnt/β-catenin signaling pathways in rat chondrocytes |
| Tao Yang et al. (2020) | Rat chondrocytes | Vitamin D3 | Wnt3a/β-catenin | Vitamin D3 and PNU-74654 could attenuate the effects induced by TNF-α and increase the level of col2a1 and aggrecan and decrease the expression of MMP-3 and MMP-13, ADAMTS-4, ADAMTS-5, Wnt-3a, and nuclear β-catenin |
| V Deshmukh et al. (2018) | SW480 cells and Sprague–Dawley rats | SM04690 | Wnt/β-catenin | SM04690 induces hMSC differentiation into chondrocytes, decreases cartilage catabolic marker levels, promotes cartilage growth, and improves joint health in a rat model of knee OA |
| Hanting Xia et al. (2020) | MIA-induced OA rat models and chondrocytes | Jiawei Yanghe decoction (JWYHD) | Wnt/β-catenin | JWYHD increases the chondrocyte viability against IL-1β-induced chondrocyte apoptosis and preserves glycosaminoglycans in the extracellular matrix. JWYHD promotes chondrocyte viability against apoptosis and decreases MMP-3, MMP-13, caspase-3, and caspase-9 via the Wnt/β-catenin signaling pathway |