Inhibition of RANKL-induced osteoclastogenesis through the suppression of the ERK signaling pathway by astragaloside IV and attenuation of titanium-particle-induced osteolysis

Li, Mingjun; Wang, Wengang; Geng, Lina; Qin, Yanru; Wu, Dong; Zhang, Xudong; Qin, An; Zhang, Mingzhi

doi:10.3892/ijmm.2015.2330

Cited by 24 publications

(26 citation statements)

References 52 publications

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“…It was found that the mRNA expression level of osteoclast-related genes decreased following the treatment with DAPT. Several previous studies reported that RANKLinduced ERK, and JNK pathway played a crucial role in the formation of osteoclast (Li et al, 2015;Liu et al, 2014), but few studies discussed the Notch signaling pathway. Notch signaling is highly conserved, and it plays an essential role in varieties of cell processes.…”

Section: Discussionmentioning

confidence: 99%

DAPT inhibits titanium particle‐induced osteolysis by suppressing the RANKL/Notch2 signaling pathway

Wei

Fan

Chen

et al. 2020

J Biomedical Materials Res

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Artificial prosthesis is wildly used in clinical medicine for degenerative disease such as osteoclast‐related diseases. However, the material wear particles released from the surface of prostheses cause prosthetic loosening as a result of aseptic osteolysis in long‐term use. Therefore, it is important to find an agent that inhibits the formation and function of osteoclast for therapeutic use. Notch signaling pathway plays a lot of roles in cell proliferation, differentiation, and apoptosis. However, the role of Notch signaling pathway in osteoclastogenesis remains unclear. The aim of this study is to assess the effects of γ‐secretase inhibitor DAPT on osteoclastogenesis via Notch signaling pathway in vitro and titanium particle‐induced osteolysis in vivo. In animal experiments, the inhibitory effect of DAPT on titanium particle‐induced osteolysis in a mouse calvaria model was demonstrated. Interestingly, few resorption pits were observed following administration of DAPT and almost no osteoclasts formed at high concentration of DAPT. in vitro experiments revealed the mechanism of the effects of DAPT on osteoclastogenesis. DAPT inhibited the formation and function of osteoclast by blocking RANKL‐induced Notch2‐NF‐κB complex signaling pathway. In conclusion, these results indicated that DAPT could prevent and cure titanium particle‐induced prosthetic loosening and other osteoclast‐related diseases.

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Section: Discussionmentioning

confidence: 99%

DAPT inhibits titanium particle‐induced osteolysis by suppressing the RANKL/Notch2 signaling pathway

Wei

Fan

Chen

et al. 2020

J Biomedical Materials Res

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“…ERK signaling pathway has been implicated in the protective effects of AS-IV in different models. AS-IV exerted potent inhibitory effects on receptor activator for nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis by suppressing ERK signaling pathway in vitro [31]. AS-IV also prevented glutamate-induced apoptosis in PC12 neuroblastic cells by blocking the phosphorylation of ERK [32].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Alleviates Lipopolysaccharide-Induced Acute Kidney Injury Through Down-Regulating Cytokines, CCR5 and p-ERK, and Elevating Anti-Oxidative Ability

Chen¹,

Zhang²

2017

Med Sci Monit

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BackgroundAstragaloside IV (AS-IV) has been shown to prevent ischemia-induced acute kidney injury (AKI) in rat models of ischemia and reperfusion. However, the effects of AS-IV on AKI during sepsis and endotoxinemia is unclear. The current study aimed to investigate the effects and molecular mechanisms of AS-IV on lipopolysaccharide (LPS)-induced AKI.Material/MethodsAdult male CD-1 mice were randomly assigned into 6 groups (n=8/group): control group: mice were intraperitoneally (i.p.) injected with normal saline; LPS group (10 mg/kg, i.p.); low-dose AS-IV (25 mg/kg; gavage for 7 days) + LPS (i.p., 1 hour after last gavage) group; medial-dose AS-IV (50 mg/kg) + LPS group; high-dose AS-IV (100 mg/kg) + LPS group; high-dose AS-IV alone (100 mg/kg; gavage for 7 days) group. Blood samples were collected at 24 hours after LPS injection, and plasma uric acid and BUN were measured with colorimetric detection kits. The concentration of plasma tumor necrosis factor (TNF)-α and interleukin 1β, renal p-extracellular signal-regulated kinases, and urinary albumin were evaluated by ELISA. The expression of CCR5 in renal tissue was evaluated by PCR and Western blotting. Concentrations of glutathione (GSH) and reactive oxygen species (ROS) in renal tissue were also measured.ResultsAS-IV decreased LPS-stimulated production of blood TNF-α and IL-6, LPS-induced the expression of CCR5, and activation of ERK in the kidneys in a rodent model of endotoxinemia. AS-IV attenuated LPS-caused decreased GSH and increased ROS. It also attenuated LPS-induced increases in plasma uric acid, BUN, and urinary albumin.ConclusionsAS-IV protects against AKI during bacterial endotoxinemia by attenuating expression of cytokines, CCR5, and p-ERK, and elevating anti-oxidative ability.

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“…During bacterial infection or trauma, dental pulp odontoblasts proliferate and differentiate to form a reparative dentine that prevents lesions . AS‐IV has been reported to affect RANKL‐induced osteoclastogenesis, and RANKL signaling is related to odontoblastic differentiation . However, whether AS‐IV participates in odontoblastic differentiation of dental pulp cells remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Due to its extensive pharmacological activities, including anti‐inflammatory, antioxidant, antitumor, and immunomodulatory effects, AS‐IV has been found to regulate a variety of pathophysiological processes . AS‐IV reportedly affects receptor activator of nuclear factor‐κB (RANKL)‐induced osteoclastogenesis and titanium particle‐induced osteolysis, suggesting that AS‐IV is a potential agent for the treatment of osteoclast‐related diseases . Intriguingly, RANKL signaling also helps to regulate odontoblast differentiation .…”

Section: Introductionmentioning

confidence: 99%

“…LPS also activates multiple signaling pathways, including the extracellular signal‐regulated kinase (ERK) and nuclear factor‐κB (NF‐κB) pathways, and produces immune responses in dental pulp cells . Intriguingly, some pharmacological activities of AS‐IV result from AS‐IV‐mediated inhibition of the ERK and NF‐κB signaling pathways . Basic fibroblast growth factor, also known as bFGF, FGF2, or FGF‐β, one of the pro‐inflammatory factors which can be induced by LPS in odontoblast‐like cells, has been reportedly involve in the regeneration and differentiation of dental pulp cells .…”

Section: Introductionmentioning

confidence: 99%

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Astragaloside IV attenuates inflammatory injury and promotes odontoblastic differentiation in lipopolysaccharide‐stimulated MDPC‐23 cells and rat pulpitis

Ding¹,

Gao

Zheng³

et al. 2019

J Oral Pathology Medicine

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Background Astragaloside IV (AS‐IV), a natural herbal compound from Astragalus membranaceus, has inhibitory effects on receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclastogenesis, and RANKL signal helps to regulate odontoblast differentiation. However, whether and how AS‐IV affects odontoblastic differentiation remains unclear. Methods Lipopolysaccharide (LPS)‐stimulated MDPC‐23 cells and rat pulpitis were treated with AS‐IV, cell viability, and LDH leakage was analyzed by CCK‐8 assay and LDH Leakage assay. The production of TNF‐α and IL‐6 was determined by ELISA and qRT‐PCR assay. The expression of alkaline phosphatase (ALP) was detected using an ALP assay kit, and the expression of dentin sialophos‐phoprotein (DSPP), dentin matrix protein‐1 (DMP1), basic fibroblast growth factor (FGF2), and phosphorylated extracellular signal‐regulated kinase (p‐ERK) was determined by western blot. Results AS‐IV dose dependently increased in cell viability and decreased the overproduction of TNF‐α and IL‐6 in LPS‐stimulated MDPC‐23 cells. AS‐IV also counteracted LPS‐induced downregulation of ALP, DSPP, and DMP1 in MDPC‐23 cells. Furthermore, AS‐IV significantly decreased the expression of FGF2 and p‐ERK in LPS‐stimulated MDPC‐23 cells. More important, the addition of FGF2 partly neutralized AS‐IV‐mediated inhibition of FGF2/ERK signaling, abolished AS‐IV‐induced reduction of TNF‐α and IL‐6, and counteracted AS‐IV‐induced upregulation of DSPP and DMP‐1 in these cells. Meanwhile, AS‐IV inhibited the excessive production of TNF‐α and IL‐6, suppressed the downregulation of DSPP and DMP1, and disturbed the up‐regulation of FGF2 and p‐ERK in the pulp tissues of rat pulpitis model. Conclusions AS‐IV exerted anti‐inflammatory and pro‐differentiation effects in LPS‐stimulated MDPC‐23 cells and rat pulpitis via inhibiting the FGF2/ERK signaling pathway.

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Inhibition of RANKL-induced osteoclastogenesis through the suppression of the ERK signaling pathway by astragaloside IV and attenuation of titanium-particle-induced osteolysis

Cited by 24 publications

References 52 publications

DAPT inhibits titanium particle‐induced osteolysis by suppressing the RANKL/Notch2 signaling pathway

DAPT inhibits titanium particle‐induced osteolysis by suppressing the RANKL/Notch2 signaling pathway

Astragaloside IV Alleviates Lipopolysaccharide-Induced Acute Kidney Injury Through Down-Regulating Cytokines, CCR5 and p-ERK, and Elevating Anti-Oxidative Ability

Astragaloside IV attenuates inflammatory injury and promotes odontoblastic differentiation in lipopolysaccharide‐stimulated MDPC‐23 cells and rat pulpitis

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