Targeting hepatic oxidative stress rescues bone loss in liver fibrosis
Objective: Chronic liver diseases often involve metabolic damage to the skeletal system. The underlying mechanism of bone loss in chronic liver diseases remains unclear, and appropriate therapeutic options, except for orthotopic liver transplantation, have proved insufficient for these patients. Thi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877822001685 |
| _version_ | 1811297266991890432 |
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| author | Soichiro Sonoda Sara Murata Haruyoshi Yamaza Ratih Yuniartha Junko Fujiyoshi Koichiro Yoshimaru Toshiharu Matsuura Yoshinao Oda Shouichi Ohga Tasturo Tajiri Tomoaki Taguchi Takayoshi Yamaza |
| author_facet | Soichiro Sonoda Sara Murata Haruyoshi Yamaza Ratih Yuniartha Junko Fujiyoshi Koichiro Yoshimaru Toshiharu Matsuura Yoshinao Oda Shouichi Ohga Tasturo Tajiri Tomoaki Taguchi Takayoshi Yamaza |
| author_sort | Soichiro Sonoda |
| collection | DOAJ |
| description | Objective: Chronic liver diseases often involve metabolic damage to the skeletal system. The underlying mechanism of bone loss in chronic liver diseases remains unclear, and appropriate therapeutic options, except for orthotopic liver transplantation, have proved insufficient for these patients. This study aimed to investigate the efficacy and mechanism of transplantation of immature hepatocyte-like cells converted from stem cells from human exfoliated deciduous teeth (SHED-Heps) in bone loss of chronic liver fibrosis. Methods: Mice that were chronically treated with CCl4 received SHED-Heps, and trabecular bone density, reactive oxygen species (ROS), and osteoclast activity were subsequently analyzed in vivo and in vitro. The effects of stanniocalcin 1 (STC1) knockdown in SHED-Heps were also evaluated in chronically CCl4 treated mice. Results: SHED-Hep transplantation (SHED-HepTx) improved trabecular bone loss and liver fibrosis in chronic CCl4-treated mice. SHED-HepTx reduced hepatic ROS production and interleukin 17 (Il-17) expression under chronic CCl4 damage. SHED-HepTx reduced the expression of both Il-17 and tumor necrosis factor receptor superfamily 11A (Tnfrsf11a) and ameliorated the imbalance of osteoclast and osteoblast activities in the bone marrow of CCl4-treated mice. Functional knockdown of STC1 in SHED-Heps attenuated the benefit of SHED-HepTx including anti-bone loss effect by suppressing osteoclast differentiation through TNFSF11–TNFRSF11A signaling and enhancing osteoblast differentiation in the bone marrow, as well as anti-fibrotic and anti-ROS effects in the CCl4-injured livers. Conclusions: These findings suggest that targeting hepatic ROS provides a novel approach to treat bone loss resulting from chronic liver diseases. |
| first_indexed | 2024-04-13T06:00:49Z |
| format | Article |
| id | doaj.art-b7ca6942984a4830954e15f94e83e0fe |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-13T06:00:49Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-b7ca6942984a4830954e15f94e83e0fe2022-12-22T02:59:26ZengElsevierMolecular Metabolism2212-87782022-12-0166101599Targeting hepatic oxidative stress rescues bone loss in liver fibrosisSoichiro Sonoda0Sara Murata1Haruyoshi Yamaza2Ratih Yuniartha3Junko Fujiyoshi4Koichiro Yoshimaru5Toshiharu Matsuura6Yoshinao Oda7Shouichi Ohga8Tasturo Tajiri9Tomoaki Taguchi10Takayoshi Yamaza11Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, JapanDepartment of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, JapanDepartment of Pediatric Dentistry, Kyushu University Graduate School of Dental Science, Fukuoka, JapanDepartment of Anatomy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, IndonesiaDepartment of Pediatrics, Kyushu University Graduate School of Medical Sciences, Fukuoka, JapanDepartment of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, JapanDepartment of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, JapanDepartment of Anatomic Pathology, Kyushu University Graduate School of Medical Sciences, Fukuoka, JapanDepartment of Pediatrics, Kyushu University Graduate School of Medical Sciences, Fukuoka, JapanDepartment of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, JapanDepartment of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan; Fukuoka College of Health Sciences, Fukuoka, JapanDepartment of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, Fukuoka, Japan; Corresponding author. Department of Molecular Cell Biology and Oral Anatomy, Kyushu University Graduate School of Dental Science, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Fax: +81 92 642 6304.Objective: Chronic liver diseases often involve metabolic damage to the skeletal system. The underlying mechanism of bone loss in chronic liver diseases remains unclear, and appropriate therapeutic options, except for orthotopic liver transplantation, have proved insufficient for these patients. This study aimed to investigate the efficacy and mechanism of transplantation of immature hepatocyte-like cells converted from stem cells from human exfoliated deciduous teeth (SHED-Heps) in bone loss of chronic liver fibrosis. Methods: Mice that were chronically treated with CCl4 received SHED-Heps, and trabecular bone density, reactive oxygen species (ROS), and osteoclast activity were subsequently analyzed in vivo and in vitro. The effects of stanniocalcin 1 (STC1) knockdown in SHED-Heps were also evaluated in chronically CCl4 treated mice. Results: SHED-Hep transplantation (SHED-HepTx) improved trabecular bone loss and liver fibrosis in chronic CCl4-treated mice. SHED-HepTx reduced hepatic ROS production and interleukin 17 (Il-17) expression under chronic CCl4 damage. SHED-HepTx reduced the expression of both Il-17 and tumor necrosis factor receptor superfamily 11A (Tnfrsf11a) and ameliorated the imbalance of osteoclast and osteoblast activities in the bone marrow of CCl4-treated mice. Functional knockdown of STC1 in SHED-Heps attenuated the benefit of SHED-HepTx including anti-bone loss effect by suppressing osteoclast differentiation through TNFSF11–TNFRSF11A signaling and enhancing osteoblast differentiation in the bone marrow, as well as anti-fibrotic and anti-ROS effects in the CCl4-injured livers. Conclusions: These findings suggest that targeting hepatic ROS provides a novel approach to treat bone loss resulting from chronic liver diseases.http://www.sciencedirect.com/science/article/pii/S2212877822001685Chronic liver diseasesHepatic osteodystrophyReactive oxidative speciesStanniocalcin 1Interleukin 17Neutrophils |
| spellingShingle | Soichiro Sonoda Sara Murata Haruyoshi Yamaza Ratih Yuniartha Junko Fujiyoshi Koichiro Yoshimaru Toshiharu Matsuura Yoshinao Oda Shouichi Ohga Tasturo Tajiri Tomoaki Taguchi Takayoshi Yamaza Targeting hepatic oxidative stress rescues bone loss in liver fibrosis Molecular Metabolism Chronic liver diseases Hepatic osteodystrophy Reactive oxidative species Stanniocalcin 1 Interleukin 17 Neutrophils |
| title | Targeting hepatic oxidative stress rescues bone loss in liver fibrosis |
| title_full | Targeting hepatic oxidative stress rescues bone loss in liver fibrosis |
| title_fullStr | Targeting hepatic oxidative stress rescues bone loss in liver fibrosis |
| title_full_unstemmed | Targeting hepatic oxidative stress rescues bone loss in liver fibrosis |
| title_short | Targeting hepatic oxidative stress rescues bone loss in liver fibrosis |
| title_sort | targeting hepatic oxidative stress rescues bone loss in liver fibrosis |
| topic | Chronic liver diseases Hepatic osteodystrophy Reactive oxidative species Stanniocalcin 1 Interleukin 17 Neutrophils |
| url | http://www.sciencedirect.com/science/article/pii/S2212877822001685 |
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