Circulating osteocrin is associated with cardiac remodeling in canine myxomatous mitral valve disease and skeletal alterations in a rat pressure-overload model
- 1Laboratory of Companion Animal Surgery, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan
- 2Yokohama Yamate Dog and Cat Medical Center, Yokohama, Kanagawa, Japan
- 3Laboratory of Clinical Pathology, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan
Abstract
Background: Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disease in dogs and is increasingly recognized as a systemic disorder associated with extracardiac remodeling. Osteocrin (OSTN), a secreted peptide implicated in natriuretic peptide biology and skeletal homeostasis, has emerged as a potential candidate biomarker of cardiovascular–skeletal interactions. However, circulating OSTN dynamics during cardiovascular disease progression remain incompletely characterized.
Methods: We employed a translational study design integrating a clinical cohort of dogs with naturally occurring myxomatous mitral valve disease (MMVD) and an experimental rat pressure-overload remodeling model. Circulating OSTN concentrations were evaluated alongside cardiac biomarkers, echocardiographic indices, bone mineral density, skeletal mechanical properties, and tissue localization by immunohistochemistry.
Results: In the canine cohort (n = 47), circulating OSTN concentrations demonstrated stage-dependent alterations and were significantly associated with echocardiographic indices of cardiac remodeling. In the rat pressure-overload model, circulating OSTN concentrations increased, whereas NT-proBNP did not show a significant pressure-overload-associated increase. In pooled analyses, circulating OSTN was inversely associated with bone mineral density and stiffness; however, these associations were substantially influenced by between-group separation, whereas no significant associations were observed between NT-proBNP and the skeletal parameters examined. Multivariable regression analysis demonstrated that ACVIM disease stage remained significantly associated with circulating OSTN concentrations after adjustment for age and body weight.
Conclusion: Circulating OSTN was associated with cardiac remodeling in dogs with MMVD and with skeletal alterations in an experimental rat pressure-overload model. These findings support further investigation of OSTN as a candidate biomarker at the interface between cardiovascular and skeletal remodeling.
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BibTeX
@article{komatsu2026circulating,
title = {{Circulating osteocrin is associated with cardiac remodeling in canine myxomatous mitral valve disease and skeletal alterations in a rat pressure-overload model}},
author = {Masafumi Komatsu and Hiromu Udagawa and Ryuji Araki and Yuji Hamamoto and Eunryel Nam and Minoru Okamoto and Mitsuhiro Isaka},
journal = {Frontiers in Veterinary Science},
year = {2026},
month = oct,
doi = {10.3389/fvets.2026.1975572},
url = {https://doi.org/10.3389/fvets.2026.1975572},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Circulating osteocrin is associated with cardiac remodeling in canine myxomatous mitral valve disease and skeletal alterations in a rat pressure-overload model
AU - Masafumi Komatsu
AU - Hiromu Udagawa
AU - Ryuji Araki
AU - Yuji Hamamoto
AU - Eunryel Nam
AU - Minoru Okamoto
AU - Mitsuhiro Isaka
PY - 2026
DA - 2026/10/22
JO - Frontiers in Veterinary Science
DO - 10.3389/fvets.2026.1975572
UR - https://doi.org/10.3389/fvets.2026.1975572
AB - Background: Myxomatous mitral valve disease (MMVD) is the most common acquired cardiac disease in dogs and is increasingly recognized as a systemic disorder associated with extracardiac remodeling. Osteocrin (OSTN), a secreted peptide implicated in natriuretic peptide biology and skeletal homeostasis, has emerged as a potential candidate biomarker of cardiovascular–skeletal interactions. However, circulating OSTN dynamics during cardiovascular disease progression remain incompletely characterized. Methods: We employed a translational study design integrating a clinical cohort of dogs with naturally occurring myxomatous mitral valve disease (MMVD) and an experimental rat pressure-overload remodeling model. Circulating OSTN concentrations were evaluated alongside cardiac biomarkers, echocardiographic indices, bone mineral density, skeletal mechanical properties, and tissue localization by immunohistochemistry. Results: In the canine cohort (n = 47), circulating OSTN concentrations demonstrated stage-dependent alterations and were significantly associated with echocardiographic indices of cardiac remodeling. In the rat pressure-overload model, circulating OSTN concentrations increased, whereas NT-proBNP did not show a significant pressure-overload-associated increase. In pooled analyses, circulating OSTN was inversely associated with bone mineral density and stiffness; however, these associations were substantially influenced by between-group separation, whereas no significant associations were observed between NT-proBNP and the skeletal parameters examined. Multivariable regression analysis demonstrated that ACVIM disease stage remained significantly associated with circulating OSTN concentrations after adjustment for age and body weight. Conclusion: Circulating OSTN was associated with cardiac remodeling in dogs with MMVD and with skeletal alterations in an experimental rat pressure-overload model. These findings support further investigation of OSTN as a candidate biomarker at the interface between cardiovascular and skeletal remodeling.
SN - 2297-1769
ER -