Dauricine Protects from LPS-Induced Bone Loss via the ROS/PP2A/NF-κB Axis in Osteoclasts

Park, Hyun-Jung; Zadeh, Malihatosadat Gholam; Suh, Jae-Hee; Choi, Hye‐Seon

doi:10.3390/antiox9070588

Cited by 20 publications

(22 citation statements)

References 41 publications

(75 reference statements)

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“…PP2A‐dependent p65 dephosphorylation inhibited the activation of NF‐κB in epithelial cells and renal cells 48 . In osteoclasts, dauricine, an isoquinoline alkaloid with anti‐inflammatory activity, suppressed lipopolysaccharide‐induced bone resorption via the ROS/PP2A/NF‐κB pathway 49 . In the present study, CTLA‐4‐Ig with high dose induced increased gene expression of PP2A.…”

Section: Discussionsupporting

confidence: 51%

Systemic administration of cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4)‐Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation

Nakane

Imamura

Hisanaga

et al. 2021

J of Periodontal Research

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Background/objectives Cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4) is a critical immunoregulatory molecule expressed on T cells. CTLA‐4 also binds to the surfaces of monocytes and macrophages, precursors of osteoclasts. Research on rheumatoid arthritis demonstrated that CTLA‐4 suppresses inflammation and bone resorption. However, its effects on alveolar bone have yet to be understood. The purpose of this study was to investigate the role and potential mechanism of CTLA‐4 in bone resorption in periodontitis. Materials and methods In vivo, the effects of systemic administration of CTLA‐4 immunoglobulin fusion protein (CTLA‐4‐Ig) on alveolar bone resorption were investigated using a periodontitis mouse model. A total of 20 C57BL/6J mice were randomly assigned to two groups according to the administration modes. Periodontitis was induced by placing a ligature around the left maxillary second molar. The contralateral tooth was left un‐ligated. In the CTLA‐4‐Ig (+) group, CTLA‐4‐Ig was administered by intraperitoneal injection at 1 and 3 days after ligature placement. Animals in the CTLA‐4‐Ig (−) group were given only phosphate‐buffered saline each time. At 5 days after ligature placement, bone resorption was assessed by micro‐computed tomography and histological examination, and the prevalence of osteoclast‐like cells was assessed by tartrate‐resistant acid phosphatase (TRAP) staining. In vitro, the effects of CTLA‐4‐Ig on osteoclasts were evaluated. Viability of RAW 264.7 cells treated with receptor activator of nuclear factor‐κB ligand (RANKL) and CTLA‐4‐Ig was tested by WST‐1 assay. Osteoclast‐like cells were enumerated by TRAP staining, and osteoclast activity was evaluated by resorption pit assay. Gene expression levels of osteoclast differentiation markers (macrophage‐colony stimulating factor receptor, carbonic anhydrase II, cathepsin K, and Trap) and protein phosphatase 2A (PP2A), a major serine‐threonine phosphatase, were assessed by quantitative real‐time polymerase chain reaction. The effect of CTLA‐4‐Ig on the nuclear factor‐κB (NF‐κB) activation was assessed by enzyme‐linked immunosorbent assay. Results In vivo, ligature‐induced bone resorption and the numbers of osteoclast‐like cells were significantly decreased by the administration of CTLA‐4‐Ig. In vitro, treatment with RANKL and CTLA‐4‐Ig had no significant effect on cell viability. CTLA‐4‐Ig significantly reduced the prevalence and activation of osteoclast‐like cells and decreased the expressions of osteoclast differentiation markers, compared with the RANKL‐treated control. CTLA‐4‐Ig significantly suppressed RANKL‐induced phosphorylation of NF‐κB p65 but increased PP2A expression. Conclusion These results suggest that CTLA‐4‐Ig abrogates bone resorption in induced periodontitis, possibly via inhibition of osteoclast differentiation and activation. The regulation of the NF‐κB pathway and PP2A expression may be one mechanism by which CTLA‐4‐Ig suppresses osteoclast behavior.

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Section: Discussionsupporting

confidence: 51%

Systemic administration of cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4)‐Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation

Nakane

Imamura

Hisanaga

et al. 2021

J of Periodontal Research

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“…Dauricine inhibited viability and induced cell apoptosis by inhibiting the PI3K/Akt pathway in renal carcinoma cells ( Zhang et al, 2018 ). Lipopolysaccharide (LPS)-induced bone loss was inhibited by dauricine as mediated via the ROS/PP2A/NF-κB axis ( Park et al, 2020 ). In a cerebral ischemia/reperfusion rat model, dauricine attenuated the inflammatory process by downregulating the expression of ICAM-1, TNF-α, and IL-1β ( Yang et al, 2007 ).…”

Section: Introductionmentioning

confidence: 99%

Dauricine Attenuates Vascular Endothelial Inflammation Through Inhibiting NF-κB Pathway

Chen

et al. 2021

Front. Pharmacol.

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Endothelial cells are the fundamental components of blood vessels that regulate several physiological processes including immune responses, angiogenesis, and vascular tone. Endothelial dysfunction contributes to the development of various diseases such as acute lung injury, and endothelial inflammation is a vital part of endothelial dysfunction. Dauricine is an extract isolated from Menispermum dauricum DC, a traditional Chinese medical plant that can be used for pharyngitis. In this work, we found that IL-1β-induced overexpression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin was inhibited by dauricine in primary human umbilical vein endothelial cells (HUVECs). Correspondingly, adhesion of human acute monocytic leukemia cell line (THP-1) to HUVECs was decreased by dauricine. Further studies showed that dauricine inhibited the activation of nuclear factor-κB (NF-κB) pathway in HUVECs stimulated with IL-1β. In vivo, dauricine protected mice from lipopolysaccharide (LPS)-induced acute lung injury. In lung tissues, the activation of NF-κB pathway and the expression of its downstream genes (ICAM-1, VCAM-1, and E-selectin) were decreased by dauricine, consistent with what was found in vitro. In summary, we concluded that dauricine could alleviate endothelial inflammation by suppressing NF-κB pathway, which might serve as an effective candidate for diseases related with endothelial inflammation.

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“…LPS can upregulate the inflammatory mediators in bone tissue (59). LPS has identified as the vital factor in inflammatoryinduced osteoclast differentiation leading to bone loss (60,61). Levels of sera IL-17A and LPS correlated with certain gut microorganisms in the OVX mice, indicating a link between immune responses and changes in gut microbiome composition.…”

Section: Discussionmentioning

confidence: 99%

Heat-Killed Lacticaseibacillus paracasei GMNL-653 Exerts Antiosteoporotic Effects by Restoring the Gut Microbiota Dysbiosis in Ovariectomized Mice

et al. 2022

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Osteoporosis is a metabolic inflammatory disease, an imbalance occurs between bone resorption and formation, leading to bone loss. Anti-inflammatory diet is considered having the potential to ameliorate osteoporosis. Heat-killed probiotics exhibit health benefits in relation to their immunomodulatory effects, but the detail mechanism involved in gut microbiota balance, host metabolism, immunity, and bone homeostasis remains unclear. In this study, we evaluated the antiosteoporotic effects of heat-killed Lacticaseibacillus paracasei GMNL-653 in vitro and in ovariectomized (OVX) mice. Furthermore, whole-genome sequencing and comparative genomics analysis demonstrated potentially genes involved in antiosteoporotic activity. The GMNL-653 exerts anti-inflammatory activity which restored gut microbiota dysbiosis and maintained intestinal barrier integrity in the OVX mice. The levels of IL-17 and LPS in the sera decreased following GMNL-653 treatment compared with those of the vehicle control; mRNA levels of RANKL were reduced and TGF-β and IL-10 enhanced in OVX-tibia tissue after treatment. The levels of IL-17 were significantly associated with gut microbiota dysbiosis. Gut microbial metagenomes were further analyzed by PICRUSt functional prediction, which reveal that GMNL-653 intervention influence in several host metabolic pathways. The analysis of whole-genome sequencing accompanied by comparative genomics on three L. paracasei strains revealed a set of GMNL-653 genes that are potentially involved in antiosteoporotic activity. Our findings validated antiosteoporotic activity of heat-killed GMNL-653 using in vitro and in vivo models, to whole-genome sequencing and identifying genes potentially involved in this gut microbiota–bone axis.

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Dauricine Protects from LPS-Induced Bone Loss via the ROS/PP2A/NF-κB Axis in Osteoclasts

Cited by 20 publications

References 41 publications

Systemic administration of cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4)‐Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation

Systemic administration of cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4)‐Ig abrogates alveolar bone resorption in induced periodontitis through inhibition of osteoclast differentiation and activation: An experimental investigation

Dauricine Attenuates Vascular Endothelial Inflammation Through Inhibiting NF-κB Pathway

Heat-Killed Lacticaseibacillus paracasei GMNL-653 Exerts Antiosteoporotic Effects by Restoring the Gut Microbiota Dysbiosis in Ovariectomized Mice

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