REPIN1 regulates iron metabolism and osteoblast apoptosis in osteoporosis

Osteoporosis is not well treated due to the difficulty of finding commonalities between the various types of it. Iron homeostasis is a vital component in supporting biochemical functions, and iron overload is recognized as a common risk factor for osteoporosis. In this research, we found that there...

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Bibliographic Details
Published in:Cell death & disease 2023-09, Vol.14 (9), p.631-631, Article 631
Main Authors: Xia, Yu, Ge, Gaoran, Xiao, Haixiang, Wu, Mingzhou, Wang, Tianhao, Gu, Chengyong, Yang, Huilin, Geng, Dechun
Format: Article
Language:English
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Animal models
Antibodies
Apoptosis
BAX protein
Bcl-2 protein
Biochemistry
Biomedical and Life Sciences
Bone loss
Cell Biology
Cell Culture
Homeostasis
Immunology
Iron
Life Sciences
Metabolism
Osteoblasts
Osteoporosis
Risk factors
Toxicity
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Summary:Osteoporosis is not well treated due to the difficulty of finding commonalities between the various types of it. Iron homeostasis is a vital component in supporting biochemical functions, and iron overload is recognized as a common risk factor for osteoporosis. In this research, we found that there is indeed evidence of iron accumulation in the bone tissue of patients with osteoporosis and REPIN1, as an origin specific DNA binding protein, may play a key role in this process. We revealed that sh- Repin1 therapy can rescue bone loss in an iron-overload-induced osteoporosis mouse model. Knockdown of Repin1 can inhibit apoptosis and enhance the resistance of osteoblasts to iron overload toxicity. REPIN1 promoted apoptosis by regulating iron metabolism in osteoblasts. Mechanistically, knockdown of Repin1 decreased the expression of Lcn2 , which ameliorated the toxic effects of intracellular iron overload. The anti-iron effect of lentivirus sh- Repin1 was partially reversed or replicated by changing LCN2 expression level via si-RNA or plasmid, which indirectly verified the key regulatory role of LCN2 as a downstream target. Furthermore, the levels of BCL2 and BAX, which play a key role in the mitochondrial apoptosis pathway, were affected. In summary, based on the results of clinical specimens, animal models and in vitro experiments, for the first time, we proved the key role of REPIN1 in iron metabolism-related osteoporosis.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-023-06160-w