IL-17A suppresses the expression of bone resorption-related proteinases and osteoclast differentiation via IL-17RA or IL-17RC receptors in RAW264.7 cells

Kitami, Satoshi; Tanaka, Hideki; Kawato, Takayuki; Tanabe, Natsuko; Katono-Tani, Tomoko; Zhang, Fan; Suzuki, Naoto; Yonehara, Yoshiyuki; Maeno, Masao

doi:10.1016/j.biochi.2009.12.011

Cited by 69 publications

(54 citation statements)

References 31 publications

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“…1). The results were in according with other studies that showed IL-17RA and RC were expressed in receptor activator of NF-κB ligand (RANKL)-stimulated RAW264.7 cells and human peripheral blood monocytes [14,15]. …”

Section: Resultssupporting

confidence: 85%

IL-17A Induces Pro-Inflammatory Cytokines Production in Macrophages via MAPKinases, NF-κB and AP-1

Chen

Liao

Gao

et al. 2013

Cell Physiol Biochem

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Background: Interleukin (IL)-17A, a newly identified cytokine, may participate in the transition of a stable plaque into an unstable plaque. Macrophages play a critical role in the destabilization of atherosclerotic plaque. Methods: RAW 264.7 cells were stimulated with IL-17A. The mRNA expression of inflammatory cytokines was determined by RT-PCR. The cytokines production in the supernatants was measured by ELISA. Small interfering RNA (siRNA) was used to confirm that IL-17A-induced pro-inflammatory cytokines production via IL-17RA signaling. The western blot assay was used to detect the phosphorylation of MAPKinases including p38 and ERK1/2. The DNA binding activity of nuclear factor NF-κB and AP-1 were detected by EMSA. Results: IL-17A induced the production of pro-inflammatory cytokines in macrophages in a time- and dose-dependent manner, such as tumor necrosis factor (TNF)-a, IL-1ß, and IL-6. Meanwhile, IL-17A resulted in the phosphorylation of p38 and ERK1/2 and increased DNA-binding activity of NF-κB and AP-1. Pharmacological inhibitors of p38 and ERK1/2 partly attenuated IL-17A-induced TNF-a, IL-1ß, and IL-6 production. Either NF-κB inhibitor or AP-1 inhibitor also partly decreased the IL-17A-induced cytokine production. Conclusions: IL-17A induces pro-inflammatory cytokines production in macrophages via MAPKinases, NF-κB and AP-1 pathway.

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Section: Resultssupporting

confidence: 85%

IL-17A Induces Pro-Inflammatory Cytokines Production in Macrophages via MAPKinases, NF-κB and AP-1

Chen

Liao

Gao

et al. 2013

Cell Physiol Biochem

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“…However, compared with the decrease in the number of osteoclasts, the addition of 1 μM nano-Pt induced little significant difference in the mRNA expression of osteoclast-associated genes and marker genes from the control. Although the mRNA expressions of osteoclast marker genes do not always correlate with the number of osteoclasts (33,34), this discrepancy indicates that other factors may be involved in the effect of nano-Pt on osteoclast differentiation. To identify such factors, we examined the expression of Nox enzymes and their partner proteins during RANKL-induced osteoclast differentiation and the effect of nano-Pt on these enzymes.…”

Section: Discussionmentioning

confidence: 99%

Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells

et al. 2011

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Abstract.Recent research has shown that platinum nanoparticles (nano-Pt) efficiently quench reactive oxygen species (ROS) as a reducing catalyst. ROS have been suggested to regulate receptor activator of NF-κB ligand (RANKL)-stimulated osteoclast differentiation. In the present study, we examined the direct effects of platinum nano-Pt on RANKL-induced osteoclast differentiation of murine pre-osteoclastic RAW 264.7 cells. The effect of the nano-Pt on the number of osteoclasts was measured and their effect on the mRNA expression for osteoclast differentiation was assayed using real-time PCR. Nano-Pt appeared to have a ROS-scavenging activity. Nano-Pt decreased the number of osteoclasts (2+ nuclei) and large osteoclasts (8+ nuclei) in a dose-dependent manner without affecting cell viability. In addition, this agent significantly blocked RANKL-induced mRNA expression of osteoclastic differentiation genes such as c-fms, NFATc1, NFATc2, and DC-STAMP as well as that of osteoclast-specific marker genes including MMP-9, Cath-K, CLC7, ATP6i, CTR, and TRAP. Although nano-Pt attenuated expression of the ROS-producing NOXfamily oxidases, Nox1 and Nox4, they up-regulated expression of Nox2, the major Nox enzyme in macrophages. These findings suggest that the nano-Pt inhibit RANKL-stimulated osteoclast differentiation via their ROS scavenging property. The use of nano-Pt as scavengers of ROS that is generated by RANKL may be a novel and innovative therapy for bone diseases.

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“…However, after 3 days of culture, as compared with the decrease in the number of osteoclasts, the mRNA expression of NFATc1 showed no significant differences when compared with controls. Although the mRNA expression of osteoclast marker genes did not always correlate with the number of osteoclasts (24,25), this discrepancy suggested that other factors may be involved in the effects of bisphosphonates on osteoclast differentiation.…”

Section: Discussionmentioning

confidence: 99%

Effects of bisphosphonates on osteoclastogenesis in RAW264.7 cells

Yoshimura

2012

Int J Mol Med

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Abstract.Bisphosphonates are used as therapeutic agents for the management of osteoporosis and other bone diseases. However, the precise effects and mechanisms of bisphosphonates on osteoclastogenesis are unclear, as previous studies have reported contradictory findings and no studies have circumstantially assessed the effects of bisphosphonates on osteoclastogenesis. Therefore, the aim of this study was to determine the effects of bisphosphonates on osteoclastogenesis in RAW264.7 (RAW) cells. To examine the direct effects of bisphosphonates on osteoclast differentiation via receptor activator of nuclear factor-κB (RANK) ligand (RANKL), RAW cells were cultured with bisphosphonates. Addition of bisphosphonates to RAW cells led to a significant decrease in the number of osteoclasts and large osteoclasts (≥8 nuclei) in a bisphosphonate concentration-dependent and time-dependent manner. The cytotoxicity of non-nitrogen-containing bisphosphonates was specific to osteoclasts, while nitrogen-containing bisphosphonates were cytotoxic and induced cell death in both osteoclasts and RAW cells. Resorption activity was significantly diminished by treatment with bisphosphonates, thus confirming that bisphosphonates impair the absorptive activity of osteoclasts. We also investigated the effects of bisphosphonates on the mRNA expression of genes associated with osteoclastogenesis, osteoclast-specific markers and apoptosis-related genes using quantitative real-time PCR. The results suggest that bisphosphonates suppress osteoclast differentiation and infusion, and induce osteoclast apoptosis. With regard to osteoclast apoptosis induced by bisphosphonates, we further investigated the detection of DNA fragmentation and Caspase-Glo 3/7 assay. DNA fragmentation was confirmed after treatment with bisphosphonates, while caspase-3/7 activity increased significantly when compared with controls. In conclusion, bisphosphonates directly inhibited RANKLstimulated osteoclast differentiation and fusion in RAW cells. It was confirmed that bisphosphonates impair osteoclast resorption activity and induce apoptosis. The effects of nonnitrogen-containing bisphosphonates were also specific to osteoclasts, while nitrogen-containing bisphosphonates were cytotoxic and induced cell death in both osteoclasts and RAW cells.

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IL-17A suppresses the expression of bone resorption-related proteinases and osteoclast differentiation via IL-17RA or IL-17RC receptors in RAW264.7 cells

Cited by 69 publications

References 31 publications

IL-17A Induces Pro-Inflammatory Cytokines Production in Macrophages via MAPKinases, NF-κB and AP-1

IL-17A Induces Pro-Inflammatory Cytokines Production in Macrophages via MAPKinases, NF-κB and AP-1

Platinum Nanoparticles Suppress Osteoclastogenesis Through Scavenging of Reactive Oxygen Species Produced in RAW264.7 Cells

Effects of bisphosphonates on osteoclastogenesis in RAW264.7 cells

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