Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity

Deng, Wei; Huang, YanBo; Li, HaiShang; Chen, ChiWei; Lin, Yuewei; Wang, Min; Huang, Huasheng; Li, Teng; Qin, Qiuli; Shao, Yang; Tang, Yi; Yuan, Kai; Ding, Jinyong; Xu, Liangliang; Li, YongXian; Zhang, Shuncong

doi:10.3389/fphar.2022.1015693

Cited by 10 publications

(11 citation statements)

References 42 publications

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“…RANK signaling is activated by RANKL via TRAF6, which, in turn, induces MAPK or NF-κB activation. Hence, the MAPK and NF-κB axes are crucial for modulating osteoclast differentiation in skeletal development and homeostasis (23)(24)(25)(26)(27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV attenuates glucocorticoid-induced osteoclastogenesis and bone loss via the MAPK/NF-κB pathway

Guo,

Li,

Yang

et al. 2023

Preprint

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Background Astragaloside IV (AS-IV) is a bioactive saponin extracted from astragalus membranaceus, and it is reported to promote osteoblast differentiation while inhibiting osteoclastogenesis. However, the mechanism of AS-IV in glucocorticoid-induced osteoclastogenesis (GIO) remains undetermined. Herein, we examined the influence of AS-IV on GIO and bone loss. Methods RAW264.7 cells were incubated with dexamethasone (Dex) alone or Dex and receptor activator of nuclear factor-B ligand (RANKL) (Dex and RANKL) for 2 days, and then treated with Dex or Dex and RANKL through AS-IV for the timeframes indicated. Following, mice were intraperitoneally administered with an intermediate-acting glucocorticoid, methylprednisolone (MP), or MP and AS-IV for 6 weeks. Results AS-IV significantly decreased Dex-induced osteoclast nucleus and area, however, it did not impact the number of Dex-induced osteoclasts in RAW264.7 cells. AS-IV also significantly decreased the osteoclastic marker protein expressions in Dex-induced RAW264.7 cells with concentration of dose dependent fashion. Additionally, AS-IV promoted p38 phosphorylation (p-) and p-p65 translocation to the nucleus, while inhibiting phosphorylation of extracellular signal-regulated kinase (ERK) (p-ERK) and inhibitor of Nuclear factor κB (NF-κB) (p-IκB) levels. However, the AS-IV-mediated action on p-MAPK, p-NF-κB, and osteoclastic marker expressions were reversed by MAPK or IκB inhibitor in Dex-induced RAW264.7 cells. Furthermore, our in vivo evaluation revealed that AS-IV also attenuated the MP-mediated bone loss, and suppressed osteoclastogenesis. Conclusions This study demonstrates that AS-IV inhibits GIO and attenuates bone loss via the MAPK/NF-κB pathway. This also suggested that AS-IV could be a potential promising therapeutic agent for glucocorticoid-triggered bone loss.

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Section: Discussionmentioning

confidence: 99%

Astragaloside IV attenuates glucocorticoid-induced osteoclastogenesis and bone loss via the MAPK/NF-κB pathway

Guo,

Li,

Yang

et al. 2023

Preprint

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“…For instance, FOXP1 facilitates osteogenic differentiation of adipose-derived mesenchymal stem cells and bone regeneration in osteoporosis [ 41 ]. Phosphorylation of MAPK14 benefits the osteogenic differentiation of human mesenchymal stem cells [ 42 ], and inhibits the osteolytic differentiation of bone marrow macrophages [ 43 ]. It is strongly indicated that M0-exo, M1-exo and M2-exo are most likely involved in the OTM process by transporting these DE-miRNAs to achieve regulation of osteogenic differentiation of hPDLSCs.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of M2 macrophage-derived exosomes facilitating osteogenic differentiation of human periodontal ligament stem cells

et al. 2022

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Background The role of periodontal ligament stem cells (PDLSCs) and macrophage polarization in periodontal tissue regeneration and bone remodeling during orthodontic tooth movement (OTM) has been well documented. Nevertheless, the interactions between macrophages and PDLSCs in OTM remain to be investigated. Consequently, the present study was proposed to explore the effect of different polarization states of macrophages on the osteogenic differentiation of PDLSCs. Methods After M0, M1 and M2 macrophage-derived exosomes (M0-exo, M1-exo and M2-exo) treatment of primary cultured human PDLSCs, respectively, mineralized nodules were observed by Alizarin red S staining, and the expression of ALP and OCN mRNA and protein were detected by RT-qPCR and Western blotting, correspondingly. Identification of differentially expressed microRNAs (DE-miRNA) in M0-exo and M2-exo by miRNA microarray, and GO and KEGG enrichment analysis of DE-miRNA targets, and construction of protein–protein interaction networks. Results M2-exo augmented mineralized nodule formation and upregulated ALP and OCN expression in PDLSCs, while M0-exo had no significant effect. Compared to M0-exo, a total of 52 DE-miRNAs were identified in M2-exo. The expression of hsa-miR-6507-3p, hsa-miR-4731-3p, hsa-miR-4728-3p, hsa-miR-3614-5p and hsa-miR-6785-3p was significantly down-regulated, and the expression of hsa-miR-6085, hsa-miR-4800-5p, hsa-miR-4778-5p, hsa-miR-6780b-5p and hsa-miR-1227-5p was significantly up-regulated in M2-exo compared to M0-exo. GO and KEGG enrichment analysis revealed that the downstream targets of DE-miRNAs were mainly involved in the differentiation and migration of multiple cells. Conclusions In summary, we have indicated for the first time that M2-exo can promote osteogenic differentiation of human PDLSCs, and have revealed the functions and pathways involved in the DE-miRNAs of M0-exo and M2-exo and their downstream targets.

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“…The effect of two compounds on cell activity was tested by a CCK8 assay according to ref. [40]. Normal cultures of RAW264.7 cells were passaged for more than 3 times, counted, and adjusted to a cell density of 1 × 10 5 cells/mL, seeded in 100 µL cell suspension per well in 96-well plates and incubated for 20 h in a 37 • C incubator.…”

Section: Cell Culture and Viability Assaymentioning

confidence: 99%

“…Inflammatory factors were detected by Griess kit or ELISA kit. RAW 264.7 cells were delivered, counted, adjusted the cell density to 3 × 10 5 cells/mL, 2 mL/well into 6-well culture plate for 20 h, grouped according to Table 1 and cultured for 20 h. After incubation, the supernatant solution was collected, centrifuged at 1200 rpm for 10 min, and the NO, TNF-α, IL-6 and IL-1β concentration in the cell supernatant was detected using the NO kit and ELISA kit according to the specification and the published papers [39,40]. To detect the expression of COX-2, iNOS, and p-p65, normally cultured RAW 264.7 cells were counted, and their cell density adjusted to 5 × 10 5 cells/mL, followed by 20 h of a 2 mL/well inoculation into 6-well culture plates.…”

Section: Assay Of Nitric Oxide Concentration Tnf-α Il-6 and Il-1βmentioning

confidence: 99%

“…Total cell RNA extraction was extracted following the instructions of the test kits The obtained total RNA was stored at −80 • C. The experiment was performed according to the SYBR Green qPCR Master Mix kit instructions and the published articles [39,40]. The reaction procedure is showed in Table 2.…”

Section: Assay Of Nitric Oxide Concentration Tnf-α Il-6 and Il-1βmentioning

confidence: 99%

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Triterpenoid and Coumarin Isolated from Astilbe grandis with Anti-Inflammatory Effects through Inhibiting the NF-κB Pathway in LPS-Induced RAW264.7 Cells

Luo,

Yue,

et al. 2023

Molecules

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The roots of Astilbe grandis, known as “Ma sang gou bang”, are used as a Miao traditional medicine with anti-inflammatory and analgesic properties. However, the active components and mechanism of action of this plant remain mostly uncharacterized. The aim of this study was to identify its active components and verify their pharmacological activity. The extract of A. grandis root was separated using various chromatographic methods. As a result, we obtained one novel triterpenoid, named astigranlactone (1), which has an unusual lactone moiety formed between C-7 and C-27. Additionally, a known coumarin compound, 11-O-galloyl bergenin (2) was isolated from this plant. The structures of these two compounds were elucidated by extensive NMR experiments in conjunction with HR-ESI-MS data. To the best of our knowledge, both compounds were isolated from this species for the first time. Moreover, we tested the anti-inflammation effect of the two compounds by establishing a cellular inflammation model induced by LPS in RAW264.7 cells. The effect of different concentrations of these compounds on the activity of RAW264.7 cells was assessed using a CCK8 assay. The levels of nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the supernatant of each group were evaluated using the Griess method and an enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time PCR (qRT-RCR) were used to measure the levels of cyclooxygenase 2 (COX-2) and nitric oxide synthase (iNOS) gene expression. Our findings revealed that these two compounds inhibited the high levels of NO, TNF-α, IL-6, IL-1β, COX-2, and iNOS (induced by LPS). Mechanistic studies demonstrated that these two compounds reduced the activation of the nuclear transcription factor-B (NF-κB) signaling pathway by inhibiting the phosphorylation of p65. Therefore, our study indicates that compounds 1 and 2 can exert a definite anti-inflammatory effect by inhibiting the NF-κB signaling pathway.

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Dehydromiltirone inhibits osteoclast differentiation in RAW264.7 and bone marrow macrophages by modulating MAPK and NF-κB activity

Cited by 10 publications

References 42 publications

Astragaloside IV attenuates glucocorticoid-induced osteoclastogenesis and bone loss via the MAPK/NF-κB pathway

Astragaloside IV attenuates glucocorticoid-induced osteoclastogenesis and bone loss via the MAPK/NF-κB pathway

Comprehensive analysis of M2 macrophage-derived exosomes facilitating osteogenic differentiation of human periodontal ligament stem cells

Triterpenoid and Coumarin Isolated from Astilbe grandis with Anti-Inflammatory Effects through Inhibiting the NF-κB Pathway in LPS-Induced RAW264.7 Cells

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