Extracellular Fe<sup>2+</sup> and Fe<sup>3+</sup> modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation
Issued Date
2023-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-85178191587
Pubmed ID
38040893
Journal Title
Scientific Reports
Volume
13
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.13 No.1 (2023)
Suggested Citation
Chankamngoen W., Krungchanuchat S., Thongbunchoo J., Sirinonthanawech N., Teerapornpuntakit J., Panupinthu N., Charoenphandhu N. Extracellular Fe<sup>2+</sup> and Fe<sup>3+</sup> modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation. Scientific Reports Vol.13 No.1 (2023). doi:10.1038/s41598-023-48436-3 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/91428
Title
Extracellular Fe<sup>2+</sup> and Fe<sup>3+</sup> modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation
Other Contributor(s)
Abstract
Iron overload negatively affects bone mass and strength. However, the impact of iron excess on osteocytes—important bone cells for mechanotransduction and remodeling—is poorly understood. Herein, we examined the effects of iron exposure on osteocytes during their maturation process. We discovered that iron overload caused apoptosis of osteocytes in early and late stages of differentiation. Notably, the expression of key proteins for iron entry was downregulated during differentiation, suggesting that mature osteocytes were less susceptible to iron toxicity due to limited iron uptake. Furthermore, iron overload also enriched a subpopulation of mature osteocytes, as indicated by increased expression of Dmp1, a gene encoding protein for bone mineralization. These iron-exposed osteocytes expressed high levels of Sost, Tnfsf11 and Fgf23 transcripts. Consistently, we demonstrated that exogenous FGF23 stimulated the formation and survival of osteoclasts, suggesting its regulatory role in bone resorption. In addition, iron overload downregulated the expression of Cx43, a gene encoding gap junction protein in the dendritic processes, and impaired YAP1 nuclear translocation in response to fluid flow in differentiated osteocytes. It can be concluded that iron overload induces cellular adaptation in differentiating osteocytes, resulting in insensitivity to mechanical stimulation and potential disruption of the balance in bone remodeling.