Iron-Chelating Agent Can Maintain Bone Homeostasis Disrupted by Iron Overload by Upregulating Wnt/Beta-Catenin Signaling

Abstract

Background. The incidence of osteoporotic fractures is increasing. In this study, we explored the activities of Wnt/β-catenin signaling in bone tissues with iron accumulation. Methods. We established rat bipedal walking models (RBWM), and a portion of our RBWM rats were intraperitoneally injected with ferric ammonium citrate, normal saline, and deferoxamine. Bone mineral density was measured with a small animal in vivo imaging system. The protein levels of ferritin, TRAP-5B, RANKL, and OPG in serum were measured by the enzyme-linked immunosorbent assay (ELISA). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to quantify the RNA and protein expression levels of certain regulators involved in Wnt/β-catenin signaling in bone tissues. Results. In the present study, we established a rat bipedal walking model containing 32 bipedal rats, which were randomly classified into four groups, termed as NS, FAC, FAC+NS, and FAC+DFO. Those three experimental groups with FAC injection had significantly lower bone mineral density (BMD) than the control group NS (P<0.05). The disruption of bone homeostasis and downregulation of Wnt/β-catenin signaling were also observed in the three groups with FAC injection. Moreover, after the injection of deferoxamine, those aberrations in samples with FAC injection seemed repaired as test results returning or getting close to normal ranges. Conclusion. The osteoporosis could be caused by iron overload, which reduced the bone mineral density by disrupting the homeostasis of bone formation and absorption and attenuating the Wnt/β-catenin signaling in bone tissues. The deferoxamine had the potential to improve the bone health by reducing the accumulation of iron and increasing the bone mass, which might be a promising therapeutic solution for osteoporosis.

Nuclear Expression of Pygo2 Correlates with Poorly Differentiated State Involving c-Myc, PCNA and Bcl9 in Myanmar Hepatocellular Carcinoma

“…The frequent activation of the signaling could be a potentially useful marker for Myanmar HCC, although the same experiment should be performed in the cases of the other countries. While our study did not directly address the mechanism that activate Wnt/β-catenin signaling in Myanmar HCC, previous studies demonstrated that iron chelators can modulate Wnt/β-catenin signaling in vitro [ 13 , 21 , 53 ]. Excess iron uptake in Myanmar could be potentially the reason for the upregulation of the signaling, as reported previously [ 2 , 40 ].…”

Lamprey immune protein triggers the ferroptosis pathway during zebrafish embryonic development

“…In addition, ferroptosis leads to myocarditis, which is associated with the pericardial edema phenotype in zebra sh (44). Simultaneously, iron imbalance can lead to abnormal bone metabolism, which is related to the spine curvature phenotype of zebra sh (45). Clari cation of the de nitive role of LIP in ferroptosis will be very helpful to our understanding of the origin and function of LIP.…”

Lamprey immune protein triggers the ferroptosis pathway during zebrafish embryonic development

“…In addition, ferroptosis leads to myocarditis, which is associated with the pericardial edema phenotype in zebrafish [ 44 ]. Simultaneously, the iron imbalance can lead to abnormal bone metabolism, which is related to the spine curvature phenotype of zebrafish [ 45 ]. Clarification of the definitive role of LIP in ferroptosis will provide insights into of the origin and dual role of LIP in immune defense and growth.…”