Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation
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 disc...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-48436-3 |
| _version_ | 1797415268272570368 |
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| author | Wasutorn Chankamngoen Saowalak Krungchanuchat Jirawan Thongbunchoo Naraporn Sirinonthanawech Jarinthorn Teerapornpuntakit Nattapon Panupinthu Narattaphol Charoenphandhu |
| author_facet | Wasutorn Chankamngoen Saowalak Krungchanuchat Jirawan Thongbunchoo Naraporn Sirinonthanawech Jarinthorn Teerapornpuntakit Nattapon Panupinthu Narattaphol Charoenphandhu |
| author_sort | Wasutorn Chankamngoen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T05:45:15Z |
| format | Article |
| id | doaj.art-9ec18af3547044098cedae3e0e9d1782 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T05:45:15Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9ec18af3547044098cedae3e0e9d17822023-12-03T12:21:33ZengNature PortfolioScientific Reports2045-23222023-12-0113111310.1038/s41598-023-48436-3Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocationWasutorn Chankamngoen0Saowalak Krungchanuchat1Jirawan Thongbunchoo2Naraporn Sirinonthanawech3Jarinthorn Teerapornpuntakit4Nattapon Panupinthu5Narattaphol Charoenphandhu6Graduate Program in Molecular Medicine, Faculty of Science, Mahidol UniversityCenter of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol UniversityCenter of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol UniversityInstitute of Molecular Biosciences, Mahidol UniversityCenter of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol UniversityCenter of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol UniversityCenter of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol UniversityAbstract 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.https://doi.org/10.1038/s41598-023-48436-3 |
| spellingShingle | Wasutorn Chankamngoen Saowalak Krungchanuchat Jirawan Thongbunchoo Naraporn Sirinonthanawech Jarinthorn Teerapornpuntakit Nattapon Panupinthu Narattaphol Charoenphandhu Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation Scientific Reports |
| title | Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation |
| title_full | Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation |
| title_fullStr | Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation |
| title_full_unstemmed | Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation |
| title_short | Extracellular Fe2+ and Fe3+ modulate osteocytic viability, expression of SOST, RANKL and FGF23, and fluid flow-induced YAP1 nuclear translocation |
| title_sort | extracellular fe2 and fe3 modulate osteocytic viability expression of sost rankl and fgf23 and fluid flow induced yap1 nuclear translocation |
| url | https://doi.org/10.1038/s41598-023-48436-3 |
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