Iron accumulation deteriorated bone loss in estrogen-deficient rats

Abstract Background Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to...

Full description

Bibliographic Details
Main Authors: Lu-lin Liu, Gong-wen Liu, Hui Liu, Kai Zhao, You-jia Xu
Format: Article
Language:English
Published: BMC 2021-08-01
Series:Journal of Orthopaedic Surgery and Research
Subjects:
Online Access:https://doi.org/10.1186/s13018-021-02663-4
_version_ 1798025237299724288
author Lu-lin Liu
Gong-wen Liu
Hui Liu
Kai Zhao
You-jia Xu
author_facet Lu-lin Liu
Gong-wen Liu
Hui Liu
Kai Zhao
You-jia Xu
author_sort Lu-lin Liu
collection DOAJ
description Abstract Background Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats. Methods In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl’s staining. The expressions of β-CTX and osteocalcin were assessed by ELISA. Results It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group. Conclusions In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption.
first_indexed 2024-04-11T18:15:31Z
format Article
id doaj.art-a3cd4422f8014485be00446158a874b0
institution Directory Open Access Journal
issn 1749-799X
language English
last_indexed 2024-04-11T18:15:31Z
publishDate 2021-08-01
publisher BMC
record_format Article
series Journal of Orthopaedic Surgery and Research
spelling doaj.art-a3cd4422f8014485be00446158a874b02022-12-22T04:09:55ZengBMCJournal of Orthopaedic Surgery and Research1749-799X2021-08-011611810.1186/s13018-021-02663-4Iron accumulation deteriorated bone loss in estrogen-deficient ratsLu-lin Liu0Gong-wen Liu1Hui Liu2Kai Zhao3You-jia Xu4Department of Orthopedics, The First Affiliated Hospital of Gannan Medical UniversitySuzhou TCM Hospital Affiliated to Nanjing University of Chinese MedicineDepartment of Orthopedics, Ganxian District Traditional Chinese Medicine Hospital of Ganzhou CityDepartment of Orthopedics, The First Affiliated Hospital of Gannan Medical UniversityDepartment of Orthopedics, Second Affiliated Hospital of Soochow UniversityAbstract Background Postmenopausal osteoporosis is characterized by an imbalance of bone resorption exceeding bone formation, resulting in a net loss of bone mass. Whether a menopause-related excess of iron contributes to the development of postmenopausal osteoporosis has remained unresolved due to a lack of an appropriate animal model. This study aimed to explore the effects of iron accumulation in bone mass in estrogen-deficient rats. Methods In the present study, ovariectomy (OVX) was performed in female rats and the changes of iron metabolism and some related modulated genes were detected. Ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. Moreover, micro-CT was performed to assess the bone microarchitecture in sham group, OVX, and FAC groups. Histological detection of iron in liver was assessed by Perl’s staining. The expressions of β-CTX and osteocalcin were assessed by ELISA. Results It was found that serum iron decreased after OVX. It was found that the expressions of Hepcidin in liver and Fpn, DMT-1 in duodenum significantly decreased at transcriptional level in OVX group than sham group. However, no difference existed in the expression of DMT-1. Then, ferric ammonium citrate (FAC) was used as a donor of iron for OVX rats. The FAC group manifested significant iron accumulation by increased serum iron and hepatic iron content. In addition, FAC treatment accelerated bone loss and decreased BMD and biomechanics in OVX rats. Moreover, bone biomarker β-CTX rather than osteocalcin increased significantly in FAC groups than OVX group. Conclusions In conclusion, no iron accumulation occurred in OVX rats. Furthermore, iron accumulation could further deteriorate osteopenia through enhanced bone resorption.https://doi.org/10.1186/s13018-021-02663-4Iron overloadOvariectomized ratOsteoporosisMicro-CTIron metabolismBiomechanical testing
spellingShingle Lu-lin Liu
Gong-wen Liu
Hui Liu
Kai Zhao
You-jia Xu
Iron accumulation deteriorated bone loss in estrogen-deficient rats
Journal of Orthopaedic Surgery and Research
Iron overload
Ovariectomized rat
Osteoporosis
Micro-CT
Iron metabolism
Biomechanical testing
title Iron accumulation deteriorated bone loss in estrogen-deficient rats
title_full Iron accumulation deteriorated bone loss in estrogen-deficient rats
title_fullStr Iron accumulation deteriorated bone loss in estrogen-deficient rats
title_full_unstemmed Iron accumulation deteriorated bone loss in estrogen-deficient rats
title_short Iron accumulation deteriorated bone loss in estrogen-deficient rats
title_sort iron accumulation deteriorated bone loss in estrogen deficient rats
topic Iron overload
Ovariectomized rat
Osteoporosis
Micro-CT
Iron metabolism
Biomechanical testing
url https://doi.org/10.1186/s13018-021-02663-4
work_keys_str_mv AT lulinliu ironaccumulationdeterioratedbonelossinestrogendeficientrats
AT gongwenliu ironaccumulationdeterioratedbonelossinestrogendeficientrats
AT huiliu ironaccumulationdeterioratedbonelossinestrogendeficientrats
AT kaizhao ironaccumulationdeterioratedbonelossinestrogendeficientrats
AT youjiaxu ironaccumulationdeterioratedbonelossinestrogendeficientrats