Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes

Abstract

The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1β were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1β-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.

hBMSC-Derived Extracellular Vesicles Attenuate IL-1β-Induced Catabolic Effects on OA-Chondrocytes by Regulating Pro-inflammatory Signaling Pathways

“…Accumulating evidence demonstrated that pro-inflammatory cytokines, such as IL-1β, TNF, and IL-6, are involved in the pathophysiology of OA (Robinson et al, 2016;Philpott et al, 2017;Urban and Little, 2018). Especially, IL-1β can act as an independent pro-inflammatory cytokine alone in promoting the progression of OA by inducing chondrocyte apoptosis and proinflammatory signaling via MAPK, NF-κB, mTOR, and PI3K/Akt signaling pathways (Moon et al, 2018;Cai et al, 2019;Zhou et al, 2019). Several reports have shown that BMSC-derived EVs play an anti-inflammatory role in OA pathophysiology through regulating MAPK, NF-κB, mTOR, and PI3K/Akt signaling pathways (Zhao et al, 2018;Sun et al, 2019;Xia et al, 2019;Zhu et al, 2019).…”

Anti-inflammation effects of the total saponin fraction from Dioscorea nipponica Makino on rats with gouty arthritis by influencing MAPK signalling pathway

“…Its main components, including dioscin, protodioscin, and pseudo protodioscin were identified by UPLC-MS [ 22 ]. In addition to its ability to reduce urate acid levels, it also has anti-inflammatory effects [ 18 , 19 , 22 ] Our newly published paper showed that RDN was effective in the treatment of GA by modulating the MAPK-PPARγ signaling pathway [ 24 ] However, it was an in vitro study that used fibroblast-like synoviocytes induced with IL-1β. The purpose of this study was to assess this mechanism using a GA rat model.…”

Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways

“…Consistent with previous research, the present study demonstrated that p38/ERK MAPK and p65/NF-κB signaling was activated in LPS-induced M1 polarization and highly expressed in synovial tissues during OA development. [37,38] Importantly, fargesin treatment did not only inhibit upregulation of p38/ERK MAPK and p65/NF-κB signaling in vivo and in vitro, but also reversed the phenotypic changes in macrophages via IL-1β-treated chondrocyte CM. This further con rmed that fargesin can inhibit the crosstalk between activated macrophages and apoptotic chondrocytes via p38/ERK MAPK and p65/NF-κB signaling during OA.…”