ArticleIn vivo (Athens, Greece)
25-Hydroxycholesterol-induced Osteoblast Oxiapoptophagy Is Involved in the Pathophysiological Process of Osteoporosis.
Article in In vivo (Athens, Greece). The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- NPC1L1 Drives Osteoporosis by Activating the C/EBPα/Cyp27a1/27-Hydroxycholesterol Axis: A Novel Therapeutic Target for Bone Loss.FASEB bioAdvances · 2025Article
- Lipids associated with autophagy: mechanisms and therapeutic targets.Cell death discovery · 2024Review
- Therapeutic Applications of Oxysterols and Derivatives in Age-Related Diseases, Infectious and Inflammatory Diseases, and Cancers.Advances in experimental medicine and biology · 2024Review
- 25-Hydroxycholesterol in health and diseases.Journal of lipid research · 2024Review
- Cytoprotective effects of α-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid and α-tocopherol on 7-ketocholesterol - Induced oxiapoptophagy: Major roles of PI3-K / PDK-1 / Akt signaling pathway and glutathione peroxidase activity in cell rescue.Current research in toxicology · 2024Article
- Impact of Oxysterols in Age-Related Disorders and Strategies to Alleviate Adverse Effects.Advances in experimental medicine and biology · 2024Review
- Role of Oxysterols in Ocular Degeneration Mechanisms and Involvement of P2X7 Receptor.Advances in experimental medicine and biology · 2024Article
- Plasma Exosomal miR-106b-5p Is Associated With Osteoporosis by TargetingIn vivo (Athens, Greece)Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aim25-hydroxycholesterol (25-HC) plays important roles in lipid metabolism, inflammatory responses, and apoptosis, but its pathophysiological association with osteoporosis (OP) has not been verified in osteoblasts. Hence, we studied the pathophysiological linkage and underlying cellular mechanisms of 25-HC in human osteoblast-like MG-63 cells and an ovariectomy-induced osteoporotic mouse model. MATERIALS AND
methodsTo investigate the pathophysiological linkage between 25-HC-induced osteoblast oxiapoptophagy and OP, 25-HC ELISA assay, MTT assay, cell live/dead staining, hematoxylin and eosin staining, DAPI staining, flow cytometry analysis, western blot, caspase-3 staining, reactive oxygen species (ROS) assay, autophagy staining, immunocytochemistry, Micro-CT image analysis and immunocytochemistry were performed in MG-63 cells and ovariectomy-induced OP animals.
resultsThe expression of cholesterol-25-hydroxylase (CH25H), an enzyme catalyzing the conversion of cholesterol to 25-HC, and the production of 25-HC were increased by lipopolysaccharide in MG-63 cells. Cytotoxicity was increased by 25-HC in MG-63 cells. Apoptosis with condensed chromatin and altered morphology was induced by 25-HC through cleavage of caspases-8, -9, and -3 in MG-63 cells. 25-HC induced oxidative stress in MG-63 cells via elevation of ROS production, cyclooxygenase-2, and inducible nitric oxide synthase. Furthermore, the expression of autophagy biomarkers, including beclin-1 and microtubule-associated protein 1A/1B-light chain 3, was elevated by 25-HC in MG-63 cells. In addition, p53 expression was increased, whereas Akt phosphorylation was suppressed in 25-HC-incubated MG-63 cells. The expression of CH25H, cleaved caspase-3, and beclin-1 were up-regulated in the femoral bone of ovariectomy-induced mouse osteoporotic animals.
conclusion25-HC plays a role in OP via the induction of oxiapoptophagic osteoblast death.
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