A Mechanistic Study of the Osteogenic Effect of Arecoline in an Osteoporosis Model: Inhibition of Iron Overload-Induced Osteogenesis by Promoting Heme Oxygenase-1 Expression.
Zhongjing JiangLinhua DengGang XiangXia XuYunjia WangPublished in: Antioxidants (Basel, Switzerland) (2024)
Iron overload-associated osteoporosis presents a significant challenge to bone health. This study examines the effects of arecoline (ACL), an alkaloid found in areca nut, on bone metabolism under iron overload conditions induced by ferric ammonium citrate (FAC) treatment. The results indicate that ACL mitigates the FAC-induced inhibition of osteogenesis in zebrafish larvae, as demonstrated by increased skeletal mineralization and upregulation of osteogenic genes. ACL attenuates FAC-mediated suppression of osteoblast differentiation and mineralization in MC3T3-E1 cells. RNA sequencing analysis suggests that the protective effects of ACL are related to the regulation of ferroptosis. We demonstrate that ACL inhibits ferroptosis, including oxidative stress, lipid peroxidation, mitochondrial damage, and cell death under FAC exposure. In this study, we have identified heme oxygenase-1 (HO-1) as a critical mediator of ACL inhibiting ferroptosis and promoting osteogenesis, which was validated by HO-1 knockdown and knockout experiments. The study links ACL to HO-1 activation and ferroptosis regulation in the context of bone metabolism. These findings provide new insights into the mechanisms underlying the modulation of osteogenesis by ACL. Targeting the HO-1/ferroptosis axis is a promising therapeutic approach for treating iron overload-induced bone diseases.
Keyphrases
- cell death
- oxidative stress
- bone mineral density
- bone regeneration
- cell cycle arrest
- diabetic rats
- mesenchymal stem cells
- postmenopausal women
- public health
- induced apoptosis
- mental health
- cell proliferation
- gene expression
- signaling pathway
- radiation therapy
- dna methylation
- cancer therapy
- transcription factor
- combination therapy
- health promotion
- iron deficiency
- endoplasmic reticulum stress
- replacement therapy