Advances in the interaction between endoplasmic reticulum stress and osteoporosis

Ming, Zhong; Wu, Zhenyu; Chen, Zhixi; Ren, Qun; Zhou, Jianguo

doi:10.1016/j.biopha.2023.115134

Cited by 6 publications

(3 citation statements)

References 177 publications

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“…The pathological development of osteoporosis can be promoted by ER stress and oxidative stress [ 14 ]. Oxysterols are cholesterol derivatives that have been shown to induce ER stress in different cell types and pathological contexts [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

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Geniposide alleviates cholesterol-induced endoplasmic reticulum stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway

Zhong,

Wu,

Chen

et al. 2024

J Orthop Surg Res

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Background Cholesterol (CHO) is an essential component of the body. However, high CHO levels in the body can damage bone mass and promote osteoporosis. CHO accumulation can cause osteoblast apoptosis, which has a negative effect on bone formation. The pathogenesis of osteoporosis is a complicate process that includes oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. Geniposide (GEN) is a natural compound with anti-osteoporotic effect. However, the roles of GEN in osteopathogenesis are still unclear. Our previous studies demonstrated that GEN could reduce the accumulation of CHO in osteoblasts and the activation of ER stress in osteoblasts. However, the molecular mechanism of GEN in inhibiting CHO-induced apoptosis in osteoblasts needs to be further investigated. Methods MC3T3-E1 cells were treated with osteogenic induction medium (OIM). Ethanol-solubilized cholesterol (100 µM) was used as a stimulator, and 10 µM and 25 µM geniposide was added for treatment. The alterations of protein expression were detected by western blot, and the cell apoptosis was analyzed by a flow cytometer. Results CHO promoted osteoblast apoptosis by activating ER stress in osteoblasts, while GEN alleviated the activation of ER stress and reduced osteoblast apoptosis by activating the GLP-1R/ABCA1 pathway. Inhibition of ABCA1 or GLP-1R could eliminate the protective activity of GEN against CHO-induced ER stress and osteoblast apoptosis. Conclusion GEN alleviated CHO-induced ER stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway.

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Section: Discussionmentioning

confidence: 99%

“…It has been shown that CHO activates ER stress [ 12 , 13 ], which promotes the development of osteoporosis [ 14 ]. Geniposide (GEN, Fig.…”

Section: Introductionmentioning

confidence: 99%

Geniposide alleviates cholesterol-induced endoplasmic reticulum stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway

Zhong,

Wu,

Chen

et al. 2024

J Orthop Surg Res

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“…The molecular pathogenesis of disuse osteoporosis is not fully understood, and ER stress may contribute to disuse-induced bone loss in the HLS mice. While ER stress has been shown to stimulate osteoblast apoptosis, increase bone loss, and promote osteoporosis development 17 , recent in-vivo studies have demonstrated the role of 4-phenyl butyrate (4-PBA) in improving bone phenotypes in certain bone diseases that involve disturbance of bone matrix such as Osteogenesis Imperfecta in the mouse model 18 .…”

Section: Introductionmentioning

confidence: 99%

Pharmacological inhibition of endoplasmic reticulum stress mitigates osteoporosis in a mouse model of hindlimb suspension

Al-Daghestani,

Qaisar,

Al Kawas

et al. 2024

Sci Rep

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Hindlimb suspension (HLS) mice exhibit osteoporosis of the hindlimb bones and may be an excellent model to test pharmacological interventions. We investigated the effects of inhibiting endoplasmic reticulum (ER) stress with 4-phenyl butyrate (4-PBA) on the morphology, physicochemical properties, and bone turnover markers of hindlimbs in HLS mice. We randomly divided 21 male C57BL/6J mice into three groups, ground-based controls, untreated HLS group and 4-PBA treated group (HLS+4PBA) (100mg/kg/day, intraperitoneal) for 21 days. We investigated histopathology, micro-CT imaging, Raman spectroscopic analysis, and gene expression. Untreated HLS mice exhibited reduced osteocyte density, multinucleated osteoclast-like cells, adipocyte infiltration, and reduced trabecular striations on micro-CT than the control group. Raman spectroscopy revealed higher levels of ER stress, hydroxyproline, non-collagenous proteins, phenylalanine, tyrosine, and CH2Wag as well as a reduction in proteoglycans and adenine. Furthermore, bone alkaline phosphatase and osteocalcin were downregulated, while Cathepsin K, TRAP, and sclerostin were upregulated. Treatment with 4-PBA partially restored normal bone histology, increased collagen crosslinking, and mineralization, promoted anti-inflammatory markers, and downregulated bone resorption markers. Our findings suggest that mitigating ER stress with 4-PBA could be a therapeutic intervention to offset osteoporosis in conditions mimicking hindlimb suspension.

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Advances in the roles of ATF4 in osteoporosis

Xiao,

Xie,

Chen

et al. 2023

Biomedicine & Pharmacotherapy

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Advances in the interaction between endoplasmic reticulum stress and osteoporosis

Cited by 6 publications

References 177 publications

Geniposide alleviates cholesterol-induced endoplasmic reticulum stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway

Geniposide alleviates cholesterol-induced endoplasmic reticulum stress and apoptosis in osteoblasts by mediating the GLP-1R/ABCA1 pathway

Pharmacological inhibition of endoplasmic reticulum stress mitigates osteoporosis in a mouse model of hindlimb suspension

Advances in the roles of ATF4 in osteoporosis

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