Circulating osteocrin is associated with cardiac remodeling in canine myxomatous mitral valve disease and skeletal alterations in a rat pressure-overload model

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.