Lipocalin-2 Regulates Osteocyte Ferroptosis and Osteocyte-Osteoblast Crosstalk via Wnt Signaling to Control Bone Formation DOI
Neha S. Dole,

Vivek Khanal,

Madeline Carroll

et al.

Published: April 29, 2025

Abstract Osteoporosis is a multifactorial disease, and emerging evidence suggests that iron overload contributes to its progression. Here, we identify Lipocalin-2 (LCN2), cytokine secreted by bone cells with endocrine effects on other tissues, as local regulator of osteocyte metabolism mediator skeletal deterioration. Our findings reveal LCN2 promotes accumulation, mitochondrial dysfunction, ferroptosis in osteocytes process dependent receptor SLC22A17. Genetic ablation Lcn2 (Dmp1-Cre; Lcn2fl/fl) mitigates their ferroptotic vulnerability preserving integrity limiting overload. Remarkably, deletion enhances dendricity lacunocanalicular network, supporting function remodeling. Mechanistically, demonstrate decreases DKK1 SOST expression bone, leading increased Wnt/β-catenin signaling osteoblast-driven formation. Using vitro vivo approaches, establish the LCN2-SLC22A17 axis key pathway linking homeostasis, These provide insight into previously unrecognized mechanism underlying iron-driven loss suggest targeting could offer therapeutic potential for osteoporosis.

Language: Английский

Lipocalin-2 Regulates Osteocyte Ferroptosis and Osteocyte-Osteoblast Crosstalk via Wnt Signaling to Control Bone Formation DOI
Neha S. Dole,

Vivek Khanal,

Madeline Carroll

et al.

Published: April 29, 2025

Abstract Osteoporosis is a multifactorial disease, and emerging evidence suggests that iron overload contributes to its progression. Here, we identify Lipocalin-2 (LCN2), cytokine secreted by bone cells with endocrine effects on other tissues, as local regulator of osteocyte metabolism mediator skeletal deterioration. Our findings reveal LCN2 promotes accumulation, mitochondrial dysfunction, ferroptosis in osteocytes process dependent receptor SLC22A17. Genetic ablation Lcn2 (Dmp1-Cre; Lcn2fl/fl) mitigates their ferroptotic vulnerability preserving integrity limiting overload. Remarkably, deletion enhances dendricity lacunocanalicular network, supporting function remodeling. Mechanistically, demonstrate decreases DKK1 SOST expression bone, leading increased Wnt/β-catenin signaling osteoblast-driven formation. Using vitro vivo approaches, establish the LCN2-SLC22A17 axis key pathway linking homeostasis, These provide insight into previously unrecognized mechanism underlying iron-driven loss suggest targeting could offer therapeutic potential for osteoporosis.

Language: Английский

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