Irisin fails to rescue bone loss in a rat model of chronic kidney disease - mineral bone disorder (CKD-MBD) but interacts with parathyroid hormone (PTH) in vivo and in vitro in IDG-SW3 osteocytes.
4 affiliations
- 1Department of Anatomy, Cell Biology, and Physiology, USA.
- 2Division of Nephrology & Hypertension, Department of Medicine, USA.
- 3Indiana Center for Musculoskeletal Health, Indiana University School of Medicine, Indianapolis, IN, USA.
- 4Roudebush VA, Indianapolis, IN, USA.
Abstract
Introduction
Chronic kidney disease progression leads to bone loss and increased fracture and mortality risk. The myokine irisin, produced by muscle during exercise, has been shown to exert protective effects on bone in healthy animals and exhibits a potential interaction with PTH in vitro. The aims of this study were to determine the effect of irisin on bone in CKD-MBD and determine if an interaction exists with PTH in vitro and in vivo.Methods
Early and mature IDG-SW3 osteocytes were treated with recombinant irisin, PTH, or both. Mineralization and osteocyte cell markers were assessed. In a similar 2 × 2 design, male Cy/+IU (CKD-MBD) rats were treated with or without irisin under high and low PTH conditions. Dynamic histomorphometry, bone structure, mechanical properties, and musculoskeletal gene markers were assessed.Results
In vitro, irisin alone downregulated Dkk1 and Sost, inhibitors of bone formation, and PTH receptor mRNA expression, primarily in early osteocytes. However, in the presence of PTH, no effects of irisin were observed. In vivo, the administration of irisin to animals with progressive CKD also downregulated PTH receptor 1 expression but did not affect bone turnover or structure or mechanical properties.Conclusions
Irisin did not meaningfully ameliorate bone loss in an animal model of CKD-MBD but did interact with PTH by downregulating its receptor in vitro in osteocytes and in vivo in bone.
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BibTeX
@article{wilson2026irisin,
title = {{Irisin fails to rescue bone loss in a rat model of chronic kidney disease - mineral bone disorder (CKD-MBD) but interacts with parathyroid hormone (PTH) in vivo and in vitro in IDG-SW3 osteocytes.}},
author = {Hannah E Wilson and Neal X Chen and Kalisha D O'Neill and Corinne E Metzger and Shruthi Srinivasan and Daniel J Stephen and Karis Blacklock and Emily K Matter and Lynda F Bonewald and Matthew R Allen and Sharon M Moe},
journal = {Bone reports},
year = {2026},
month = oct,
doi = {10.1016/j.bonr.2026.101956},
url = {https://europepmc.org/article/MED/42908875},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Irisin fails to rescue bone loss in a rat model of chronic kidney disease - mineral bone disorder (CKD-MBD) but interacts with parathyroid hormone (PTH) in vivo and in vitro in IDG-SW3 osteocytes.
AU - Hannah E Wilson
AU - Neal X Chen
AU - Kalisha D O'Neill
AU - Corinne E Metzger
AU - Shruthi Srinivasan
AU - Daniel J Stephen
AU - Karis Blacklock
AU - Emily K Matter
AU - Lynda F Bonewald
AU - Matthew R Allen
AU - Sharon M Moe
PY - 2026
DA - 2026/10/05
JO - Bone reports
DO - 10.1016/j.bonr.2026.101956
UR - https://europepmc.org/article/MED/42908875
AB - Introduction Chronic kidney disease progression leads to bone loss and increased fracture and mortality risk. The myokine irisin, produced by muscle during exercise, has been shown to exert protective effects on bone in healthy animals and exhibits a potential interaction with PTH in vitro. The aims of this study were to determine the effect of irisin on bone in CKD-MBD and determine if an interaction exists with PTH in vitro and in vivo.Methods Early and mature IDG-SW3 osteocytes were treated with recombinant irisin, PTH, or both. Mineralization and osteocyte cell markers were assessed. In a similar 2 × 2 design, male Cy/+IU (CKD-MBD) rats were treated with or without irisin under high and low PTH conditions. Dynamic histomorphometry, bone structure, mechanical properties, and musculoskeletal gene markers were assessed.Results In vitro, irisin alone downregulated Dkk1 and Sost, inhibitors of bone formation, and PTH receptor mRNA expression, primarily in early osteocytes. However, in the presence of PTH, no effects of irisin were observed. In vivo, the administration of irisin to animals with progressive CKD also downregulated PTH receptor 1 expression but did not affect bone turnover or structure or mechanical properties.Conclusions Irisin did not meaningfully ameliorate bone loss in an animal model of CKD-MBD but did interact with PTH by downregulating its receptor in vitro in osteocytes and in vivo in bone.
SN - 2352-1872
ER -