Dataset Information

Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.

ABSTRACT: Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle-induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl₆V₄ particles-induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl₆V₄ particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α-XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle-induced osteolysis and highlight the IRE1α-XBP1s pathway as a potential therapeutic target for preventing aseptic loosening.

SUBMITTER: Yu X

PROVIDER: S-EPMC11223082 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.

Yu Xin X Ren Zhengrong Z Wang Yuxiang Y Yuan Guodong G Hu Jianlun J Song Lin L Pan Cheng C Feng Kangkang K Liu Yuqiao Y Shao Longgang L Zhang Li L Wang Jinjuan J Zhao Jianning J Bao Nirong N Sun Zhongyang Z

The Journal of biological chemistry 20240518 6

Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle-induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempf ...[more]

PMID: 38768813

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Project description:Gastric cancer is a disease that occurs in the digestive system of humans and remains a problem in the medical field. Wogonoside, a natural flavonoid, has been reported to exert antitumor effects on various types of tumors. However, the effects of wogonoside on gastric cancer remain elusive. The aim of the present study was to detect whether wogonoside treatment could induce apoptosis and ER stress in gastric cancer cells. In the present study, CCK-8 assay was used to detect the cell viability, Annexin V/PI staining was used to detect the cells apoptosis, western blot analysis and real-time PCR analysis was used to detect the endoplasmic reticulum (ER) stress in the AGS and MKN-45 gastric cancer cell lines. Wogonoside treatment reduced the viability of AGS and MKN-45 cells and induced apoptosis. Furthermore, the expression level of caspase-3 and -9 significantly increased following wogonoside treatment compared with that in non-treated cells, and the protein expression levels of proapoptotic Bax and antiapoptotic Bcl-2 increased and decreased, respectively compared with that in the control group. In addition, the phosphorylated protein expression levels of mitogen-activated protein kinase kinase 5 (ASK1) and JNK increased following wogonoside treatment, and the protein expression levels of tumor necrosis factor receptor-associated factor 2 (TRAF2) and serine/threonine-protein kinase/endoribonuclease IRE1 (IRE1α) were also increased following treatment with 50 µM wogonoside for 48 h. Furthermore, the interactions between IRE1α, TRAF2 and ASK1 significantly increased following wogonoside treatment, suggesting that wogonoside induced endoplasmic reticulum (ER) stress in the AGS and MKN-45 cell lines. In addition, small interfering RNA-mediated silencing of IRE1α suppressed the activity of the IRE1α-TRAF2-ASK1 complex and prevented wogonoside-induced cell apoptosis. In conclusion, the results of the present study suggested that wogonoside exhibited antitumor activity by inducing ER stress-associated cell death through the IRE1α-TRAF2-ASK1 pathway.

Project description:Objective: Changes in bile acids (BAs) are increasingly recognized as potential targets for non-alcoholic steatohepatitis (NASH). Kaempferol has been proved to be anti-inflammatory and reduce the disorder of lipid metabolism. In order to analyze the BA profile in NASH mice and determine the predictive biomarkers of kaempferol treatment, serum-targeted metabolomics and liver tissue RNA sequencing (RNA-seq) were carried out. Design: Six normal control mice (NC group), eight HFD-fed mice (HFD group), and eight kaempferol-treated HFD-fed mice (HFD + KP group) were included in the present study. Ultra-performance liquid chromatography coupled to a tandem mass spectrometry system (UPLC-MS/MS) was used to quantify serum and liver BAs, and RNA-seq was used to quantify liver differentially expressed genes related to BA metabolism. Results: The serum levels of CA, βMCA, UDCA, and 12-DHCA, as well as ωMCA in both the serum and liver, were significantly decreased in the HFD group compared with those in the NC group, and kaempferol can increase the serum levels of βMCA, UDCA, and ωMCA and the liver level of 12-DHCA. The serum levels of TDCA, THDCA, TUDCA, TDCA/CA, and TDCA/DCA were significantly increased in the HFD group compared with those of the NC group, and kaempferol can decrease them. Furthermore, NASH mice had a higher liver level of total CA%, total CDCA%, primary BAs/secondary BAs, 12α-OH BAs/non-12α-OH Bas, and conjugated BAs/unconjugated BAs, and all decreased after kaempferol treatment. According to the RNA-seq results, we found that compared with the NC group, the mRNA expression of cholesterol-7α-hydroxylase (CYP7A1) in the HFD group was significantly increased, and the mRNA expression of sterol 12α-hydroxylase (CYP8B1) and multidrug resistance-related protein 3 (MRP3) was significantly decreased, while kaempferol significantly promoted the mRNA expression of mitochondrial sterol 27-hydroxylase (CYP27A1) and Na+ -taurocholate cotransporting polypeptide (NTCP). Conclusion: βMCA, CA, UDCA, 12-DHCA, ωMCA, CDCA, TωMCA, TDCA, THDCA, TCDCA, and TUDCA in the serum, as well as 6,7-diketoLCA, 12-DHCA, and ωMCA in the liver, may be potential biomarkers for kaempferol to improve NASH. HFD-induced NASH may be associated with the increase of CYP7A1 and the decrease of CYP8B1, leading to increased BA synthesis, and the decrease of MRP3 leading to decreased BA synthesis, and kaempferol may alleviate NASH by increasing CYP27A1 and NTCP to enhance BA transport.

Dataset Information

Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.

Publications

Kaempferol attenuates particle-induced osteogenic impairment by regulating ER stress via the IRE1α-XBP1s pathway.

Similar Datasets

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