Isoliquiritigenin (ISL), a natural flavonoid extracted from licorice, has been demonstrated to exert attenuation of the nuclear factor-κB (NF-κB) signaling pathway and anti-inflammatory activity in a wide variety of cells. In the present study, the authors first evaluated the effects of ISL on cartilage degeneration in interleukin-1β (IL-1β)-stimulated chondrocyte-like ATDC5 cells and in a mouse model of osteoarthritis (OA). The data of a cell counting kit-8 and flow cytometry assay indicated that ISL suppressed the inhibitory effect of IL-1β on cell viability. The mRNA and protein expression levels of cyclooxygenase-2 and matrix metalloproteinase-13 were significantly decreased, while the expression of collagen II was increased, as indicated by RT-qPCR and western blot analysis following the chondrocyte-like ATDC5 cells were co-intervened with IL-1β and ISL for 48 h. Also, ISL attenuated protein expressions level of pro-apoptotic Bax, cleaved-caspase-3 and cleaved-caspase-9 and promoted expression of anti-apoptotic Bcl-2. Moreover, ISL inhibited NF-κB p65 phosphorylation induced by IL-1β. In addition, ISL also increased improved the thickness of hyaline cartilage and the production of proteoglycans in the cartilage matrix in a mouse OA model. These results indicated that ISL exerted anti-inflammatory and anti-apoptotic effects on IL-1β-stimulated chondrocyte-like ATDC5 cells, which may be associated with the downregulation of the NF-κB signaling pathway. In this way, the data supported the conclusion that ISL may be a novel potential preventive agent suitable for use in OA therapy.

Isoliquiritigenin (ISL), a natural flavonoid extracted from licorice, has been demonstrated to exert attenuation of osteoclastogenesis and anti-angiogenesis activity in a wide variety of cells. Here, we first evaluated the effects of ISL on pathogenesis of osteoarthritis in a mouse model of OA. The data showed that ISL blunted progression of OA and lowered the Osteoarthritis Research Society International (OARSI)-Modified Making Score and protected the articular cartilage. The thickness of calcified cartilage zone was significantly decreased in ISL-treated ACLT mice compared with vehicle group. ISL increased expression level of lubricin and decreased collagen X (Col X), matrix metalloproteinase-13 (MMP-13). Moreover, ISL reduced aberrant active subchondral bone remodelling, including lowered trabecular pattern factor (Tb.pf) and increased bone volume/tissue volume (BV/TV, %) and thickness of subchondral bone plate (SBP) compared with vehicle-treated group. The results of immunostaining further revealed that ISL directly reduced RANKL-RANK-TRAF6 singling pathway induced osteoclastogenesis, prevented abnormal bone formation through indirect inhibition of TGF-β release. Additionally, ISL exerts anti-angiogenesis effects in subchondral bone through direct suppression of MMP-2. These results indicated that ISL attenuates progression of OA by inhibition of bone resorption and angiogenesis in subchondral bone, indicating that this may be a potential preventive therapy for OA.

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Osteoarthritis (OA) is a common and debilitating joint disease worldwide without interventions available to reverse its progression. Artesunate (ART), an anti-malaria agent, possesses diverse biological activities, including the inhibition of osteoclastogenesis and angiogenesis in various cells, but its role in subchondral bone during OA progression is not known. Here, we explored the curative effects of ART on the pathogenesis of OA in anterior cruciate ligament transection (ACLT) mice models. We found that ART attenuated articular cartilage degeneration, defined by lowered histologic scoring of OA and retarded calcification of the cartilage zone. Moreover, ART improved the expression of lubricin and aggrecan and reduced the expression of collagen X (Col X) and matrix metalloproteinase-13 (MMP-13). In parallel, ART normalized abnormal subchondral bone remodeling by maintaining bone volume fraction (BV/TV) and subchondral bone plate thickness (SBP Th) and reducing trabecular pattern factor (Tb.pf) compared to the vehicle-treated mice. Our results indicated that ART suppressed osteoclastic bone resorption through regulating RANKL-OPG system, restored coupled bone remodeling by indirectly inhibiting TGF-β/Smad2/3 signaling. Additionally, ART abrogated CD31 hi Emcn hi vessel formation via downregulating the expression of vascular endothelial growth factor (VEGF) and angiogenin-1 in subchondral bone. In conclusion, ART attenuates ACLT-induced OA by blocking bone resorption and CD31 hi Emcn hi vessel formation in subchondral bone, indicating that this may be a new therapeutic alternative for OA.

Osteoarthritis (OA) is a progressive and degenerative joint disorder that is highly prevalent worldwide and for which there is currently no effective medical therapy. Artesunate (ART), a natural compound used to treat malaria, possesses diverse biological properties, including the regulation of inflammation and apoptosis in various cells; however, its role in OA remains unclear. The aim of the present study was to investigate the effects of ART on interleukin (IL)-1β-induced chondrocyte-like ATdc5 cells and in an OA mouse model. The results revealed that ART dose-dependently relieved the inhibitory effect of IL-1β on cell viability. Moreover, ART significantly reduced the overexpression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-5 and cyclooxygenase-2 at both the gene and protein levels in chondrocyte-like ATdc5 cells stimulated by IL-1β. Furthermore, ART decreased the expression of pro-apoptotic Bax, cleaved caspase-3 and cleaved caspase-7 in a dose-dependent manner, and increased the expression of the anti-apoptotic factor Bcl-2. These changes were mediated by the inhibitory effect of ART on the nuclear factor-κB signaling pathway, defined as repression of the phosphorylation of IκBα and p65, and improved redistribution of p65. Additionally, ART blocked the advancement of the calcified cartilage zone and the loss of proteoglycan, and lowered histological scoring of OA in a mouse model. Taken together, these results indicate that ART may be of value as a therapeutic agent for OA.