Melatonin inhibits osteoclastogenesis via <scp>RANKL</scp>/<scp>OPG</scp> suppression mediated by <scp>Rev‐Erbα</scp> in osteoblasts

Tian, Yihao; Ming, Jian

doi:10.1111/jcmm.17440

Cited by 8 publications

(5 citation statements)

References 84 publications

(141 reference statements)

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“…Recently, Th17 cells have been implicated as the primary drivers of immune cell activation and cytokine production [60]. Furthermore, they are primarily responsible for inducing RANKL production by FLSs and osteoblasts, thereby promoting osteoclastogenesis [78]. Presently, the data suggest that monocyte activation occurs within the circulation of individuals with RA.…”

Section: Discussionmentioning

confidence: 99%

“…FLSs are the resident cells presenting in the intimal lining of the synovium along with resident macrophages, which are synoviocytes of type A. FLSs are highly proliferated in the synovial tissue, thus stimulating the hyperplasia of the synovium and damage to the joints. FLSs express RANKL and participate in the differentiation of osteoclasts and bone erosion [78]. CCL2 and CX3CL1 are FLS chemokines and behave as chemoattractants for monocytes/macrophages.…”

Section: Monocyte Interactions With Other Cellsmentioning

confidence: 99%

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Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis

Salnikova,

Nikiforov,

Postnov

et al. 2024

Diseases

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Rheumatoid arthritis (RA) is a chronic, systemic, and inflammatory autoimmune condition characterized by synovitis, pannus formation (with adjacent bone erosion), and joint destruction. In the perpetuation of RA, fibroblast-like synoviocytes (FLSs), macrophages, B cells, and CD4+ T-cells—specifically Th1 and Th17 cells—play crucial roles. Additionally, dendritic cells, neutrophils, mast cells, and monocytes contribute to the disease progression. Monocytes, circulating cells primarily derived from the bone marrow, participate in RA pathogenesis. Notably, CCR2 interacts with CCL2, and CX3CR1 (expressed by monocytes) cooperates with CX3CL1 (produced by FLSs), facilitating the migration involved in RA. Canonical “classical” monocytes predominantly acquire the phenotype of an “intermediate” subset, which differentially expresses proinflammatory cytokines (IL-1β, IL-6, and TNF) and surface markers (CD14, CD16, HLA-DR, TLRs, and β1- and β2-integrins). However, classical monocytes have greater potential to differentiate into osteoclasts, which contribute to bone resorption in the inflammatory milieu; in RA, Th17 cells stimulate FLSs to produce RANKL, triggering osteoclastogenesis. This review aims to explore the monocyte heterogeneity, plasticity, antigenic expression, and their differentiation into macrophages and osteoclasts. Additionally, we investigate the monocyte migration into the synovium and the role of their cytokines in RA.

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Section: Discussionmentioning

confidence: 99%

Section: Monocyte Interactions With Other Cellsmentioning

confidence: 99%

Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis

Salnikova,

Nikiforov,

Postnov

et al. 2024

Diseases

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“…They were scanned and photographed with an optical microscope (Olympus BX53, Olympus, Japan) [ 28 ]. The cell medium was washed with phosphate buffer solution, it was fixed with paraformaldehyde for 15 min, and the TRAP working liquid was added to the water bath for 60 min, the nucleus was stained with hematoxylin for 10 min, and the cells were washed twice with PBS [ 29 ]. In this study, TRAP dyeing kit (catalog number D023-1-1) produced by Nanjing Jiancheng Bioengineering Institute was used.…”

Section: Methodsmentioning

confidence: 99%

Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway

Liu,

Liao,

Shao

et al. 2024

Chin Med

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Background Angelicin, which is found in Psoralea, can help prevent osteoporosis by stopping osteoclast formation, although the precise mechanism remains unclear. Methods We evaluated the effect of angelicin on the oxidative stress level of osteoclasts using ovariectomized osteoporosis model rats and RAW264.7 cells. Changes in the bone mass of the femur were investigated using H&E staining and micro-CT. ROS content was investigated by DHE fluorescence labelling. Osteoclast-related genes and proteins were examined for expression using Western blotting, immunohistochemistry, tartrate-resistant acid phosphatase staining, and real-time quantitative PCR. The influence of angelicin on osteoclast development was also evaluated using the MTT assay, double luciferin assay, chromatin immunoprecipitation, immunoprecipitation and KAT6A siRNA transfection. Results Rats treated with angelicin had considerably higher bone mineral density and fewer osteoclasts. Angelicin prevented RAW264.7 cells from differentiating into osteoclasts in vitro when stimulated by RANKL. Experiments revealed reduced ROS levels and significantly upregulated intracellular KAT6A, HO-1, and Nrf2 following angelicin treatment. The expression of genes unique to osteoclasts, such as MMP9 and NFATc1, was also downregulated. Finally, KAT6A siRNA transfection increased intracellular ROS levels while decreasing KAT6A, Nrf2, and HO-1 protein expression in osteoclasts. However, in the absence of KAT6A siRNA transfection, angelicin greatly counteracted this effect in osteoclasts. Conclusions Angelicin increased the expression of KAT6A. This enhanced KAT6A expression helps to activate the Nrf2/HO-1 antioxidant stress system and decrease ROS levels in osteoclasts, thus inhibiting oxidative stress levels and osteoclast formation.

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“…It is noteworthy that miR-574-5p can release Rheumatoid Arthritis by exerting an impact on TLR 7/8 to induce osteoclast differentiation (Hegewald et al 2020). Besides, melatonin inhibits osteoclastogenesis in osteoblasts via the miR-882/Rev-Erbα axis (Tian et al 2022). The result of circRNA-seq showed chr8_84771783_84779275_-was down-regulated in p75NTR (-/-) EMSCs, which indicates that chr8_84771783_84779275_-may promote the activity of osteoclast during the development of EMSCs by suppressing miR-574-5p and miR-882.…”

Section: Qrt-pcr Validation Of Differentially Expressed Circrnasmentioning

confidence: 99%

Comprehensive analysis of circRNA expression profiles in p75NTR-knockout ecto- mesenchymal stem cells

Wan

Shao

et al. 2023

Preprint

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Neural crest-derived ecto-mesenchymal stem cells (EMSCs), as the progenitor cells of odontogenic stem cells, may be the suitable seed cell for regenerative dentistry. p75NTR, as the neural crest stem cell marker, plays a crucial role during the teeth development of EMSCs. Nevertheless, the interaction networks p75NTR connecting with odonto/osteogenic differentiation and mineralization are still poorly studied. Circular RNAs (circRNAs) regulate life processes mainly by performing as a competitive endogenous RNA (ceRNA) to prevent the process that microRNAs (miRNAs) bind with their target mRNAs. But the roles of p75NTR-related circRNAs in EMSCs are largely unknown. We used circRNA-seq to examine the differentially expressed circRNAs between WT and p75NTR (-/-) EMSCs and three of them were selected for qRT-PCR verification. GO, KEGG and Reactome enrichment analyses showed that differentially expressed circRNAs interact with cell proliferation, locomotory behavior, cell differentiation and are mainly involved in Wnt, JAK/STAT, Hippo and TGF-β signaling pathways. Then, CCK8, transwell assay and ALP staining assay were performed to verify the result of enrichment analyses. Then, the circRNA-miRNA interaction networks were constructed by using bioinformatics analysis. A new circRNA, mmu_circ_0001380 and mmu_circ_0013536 were selected to predict potential target miRNAs. Besides, with TargetScan, we noticed that these three circRNAs may influence the expression of DSPP and RUNX2 and qRT-PCR was performed for verification. Therefore, these three circRNAs are inclined to be vital in developing EMSCs and be novel core molecules for the further understanding of odontogenesis related to p75NTR.

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Melatonin inhibits osteoclastogenesis via RANKL/OPG suppression mediated by Rev‐Erbα in osteoblasts

Cited by 8 publications

References 84 publications

Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis

Target Role of Monocytes as Key Cells of Innate Immunity in Rheumatoid Arthritis

Angelicin improves osteoporosis in ovariectomized rats by reducing ROS production in osteoclasts through regulation of the KAT6A/Nrf2 signalling pathway

Comprehensive analysis of circRNA expression profiles in p75NTR-knockout ecto- mesenchymal stem cells

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