β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways

Park, Gyeong Do; Cheon, Yoon‐Hee; Eun, So Young; Lee, Chang Hoon; Lee, Myeung Su; Kim, Ju-Young; Cho, Hae Joong

doi:10.3390/molecules26092665

Cited by 5 publications

(6 citation statements)

References 32 publications

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“…TNF-α can decrease the efflux of cholesterol in mouse osteocyte cell line MLO-Y4 by inhibiting the expression of ABCA1 [ 44 ]. Nuclear factor-κB (NF-κB) and receptor activator of NF-κB ligand (RANKL) have been implicated in osteogenic inhibition and osteoclast differentiation, promoting the development of OP [ 45 ]. Thus, it can be postulated that upregulation of ABCA1 may exhibit protective activities against OP by promoting cholesterol efflux.…”

Section: Discussionmentioning

confidence: 99%

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

Zheng

Xiao

Zhang

et al. 2021

Cells

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Background: Overexposure to glucocorticoid (GC) produces various clinical complications, including osteoporosis (OP), dyslipidemia, and hypercholesterolemia. Geniposide (GEN) is a natural iridoid compound isolated from Eucommia ulmoides. Our previous study found that GEN could alleviate dexamethasone (DEX)-induced differentiation inhibition of MC3T3-E1 cells. However, whether GEN protected against Dex-induced cholesterol accumulation in osteoblasts was still unclear. Methods: DEX was used to induce rat OP. Micro-CT data was obtained. The ALP activity and mineralization were determined by the staining assays, and the total intracellular cholesterol was determined by the ELISA kits. The protein expression was detected by western blot. Results: GEN ameliorated Dex-induced micro-structure damages and cell differentiation inhibition in the bone trabecula in rats. In MC3T3-E1 cells, Dex enhanced the total intracellular cholesterol, which reduced the activity of cell proliferation and differentiation. Effectively, GEN decreased DEX-induced cholesterol accumulation, enhanced cell differentiation, and upregulated the expression of the GLP-1R/ABCA1 axis. In addition, inhibition of ABAC1 expression reversed the actions of GEN. Treatment with Exendin9-39, a GLP-1R inhibitor, could abrogate the protective activity of GEN. Conclusions: GEN ameliorated Dex-induced accumulation of cholesterol and inhibition of cell differentiation by mediating the GLP-1R/ABCA1 axis in MC3T3-E1 cells.

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Section: Discussionmentioning

confidence: 99%

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

Zheng

Xiao

Zhang

et al. 2021

Cells

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“…Park et al found that β-boswellic acid (βBA), a natural compound found in Boswellia serrata , significantly inhibited the phosphorylation of Btk and PLCγ2. It also reduced the expression of NFATc1 at both mRNA and protein levels, resulting in the attenuation of osteoclast differentiation and formation (Park et al 2021 ). Jeong et al discovered that betulinic acid (BA), a natural plant-derived pentacyclic triterpenoid compound, effectively inhibited osteoclastogenesis by suppressing the phosphorylation of the PLCγ2-Ca 2+ signaling pathway (Jeong et al 2020a ).…”

Section: The Ca 2+ -Related Co-stimulation Signali...mentioning

confidence: 99%

Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets

Zheng,

Liu,

Deng

et al. 2024

Mol Med

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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by inflammation of the synovial tissue and joint bone destruction, often leading to significant disability. The main pathological manifestation of joint deformity in RA patients is bone destruction, which occurs due to the differentiation and proliferation of osteoclasts. The transcription factor nuclear factor-activated T cell 1 (NFATc1) plays a crucial role in this process. The regulation of NFATc1 in osteoclast differentiation is influenced by three main factors. Firstly, NFATc1 is activated through the upstream nuclear factor kappa-B ligand (RANKL)/RANK signaling pathway. Secondly, the Ca2+-related co-stimulatory signaling pathway amplifies NFATc1 activity. Finally, negative regulation of NFATc1 occurs through the action of cytokines such as B-cell Lymphoma 6 (Bcl-6), interferon regulatory factor 8 (IRF8), MAF basic leucine zipper transcription factor B (MafB), and LIM homeobox 2 (Lhx2). These three phases collectively govern NFATc1 transcription and subsequently affect the expression of downstream target genes including TRAF6 and NF-κB. Ultimately, this intricate regulatory network mediates osteoclast differentiation, fusion, and the degradation of both organic and inorganic components of the bone matrix. This review provides a comprehensive summary of recent advances in understanding the mechanism of NFATc1 in the context of RA-related bone destruction and discusses potential therapeutic agents that target NFATc1, with the aim of offering valuable insights for future research in the field of RA. To assess their potential as therapeutic agents for RA, we conducted a drug-like analysis of potential drugs with precise structures.

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“…Absorbance was measured at 450 nm at 1-h intervals. The sample treatment period was determined based on previous studies (21)(22)(23).…”

Section: Collection Of Bone Marrow-derived Macrophages (Bmm)mentioning

confidence: 99%

Anti‑osteoclastogenic effect of fermented mealworm extract by inhibiting RANKL‑induced NFATc1 action

Ham,

Lee

2024

Exp Ther Med

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Augmented osteoclast activity and differentiation can lead to destructive bone diseases, such as arthritis and osteoporosis. Therefore, modulating osteoclastogenesis and differentiation may serve to be a possible strategy for treating such diseases. Tenebrio molitor larvae, also known as mealworms, are considered a good source of protein with nutritional value, digestibility, flavor and functional properties, such as antioxidant, anti-diabetic and anti-obesity effects. However, the role of mealworms in osteoclastogenesis remains poorly understood. The present study therefore investigated the effects of fermented mealworm extract (FME) on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs) whilst also attempting to understand the underlying mechanism, if any. The cells treated with RANKL were used as the negative control. To prepare FME, defatted mealworm powder was fermented with a Saccharomyces cerevisiae strain, and then extracted with fermented alcohol. Cell viability of BMMs isolated from 5-week-old Institute of Cancer Research mice was measured using Cell Counting Kit-8 assay. Subsequently, the effects of FME on osteoclast differentiation were measured using tartrate-resistant acid phosphatase (TRAP) staining. In addition, expression of markers associated with osteoclast differentiation was assessed by reverse transcription-quantitative PCR. Expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) was assessed by western blotting. TRAP staining revealed that FME inhibited osteoclast differentiation in a dose-dependent manner (10-100 µg/ml) without causing cytotoxicity. Specifically, the formation of osteoclasts appear to have been suppressed by FME as indicated by the reduction in the number of TRAP-positive multinucleated cells observed. Furthermore, FME treatment significantly decreased the mRNA expression of c-Fos, whilst also significantly decreasing the expression of NFATc1 on both protein and mRNA levels. c-Fos and NFATc1 are transcription factors that can regulate osteoclast differentiation. FME treatment also reduced the expression of genes associated with osteoclast differentiation and function, including dendritic cell-specific transmembrane protein , osteoclast associated Ig-like receptor , Cathepsin K and TRAP , compared with that in the control group. Subsequently, FME was found to effectively suppress RANKL-induced osteoclast differentiation compared with that by the non-fermented mealworm extract. These findings suggest that FME may confer anti-osteoclastogenic effects, providing insights into its potential application in treatment of osteoporosis.

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β-Boswellic Acid Inhibits RANKL-Induced Osteoclast Differentiation and Function by Attenuating NF-κB and Btk-PLCγ2 Signaling Pathways

Cited by 5 publications

References 32 publications

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

Geniposide Ameliorated Dexamethasone-Induced Cholesterol Accumulation in Osteoblasts by Mediating the GLP-1R/ABCA1 Axis

Recent advances of NFATc1 in rheumatoid arthritis-related bone destruction: mechanisms and potential therapeutic targets

Anti‑osteoclastogenic effect of fermented mealworm extract by inhibiting RANKL‑induced NFATc1 action

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