A Hypothalamic Oxytocinergic-Sympathetic Axis Couples Anxiety Dysregulation With Impaired Tendon-Bone Repair.

Translational multiscale study integrating clinical neuroimaging, imaging transcriptomics, and mechanistic animal experiments.

“Here, by integrating clinical neuroimaging, imaging transcriptomics, and mechanistic animal experiments, we identify hypothalamic paraventricular nucleus (PVN) oxytocinergic (OXT) neurons as a critical central node coordinating emotional regulation and bone–tendon interface (BTI) repair.”

Patients with rotator cuff injury (RCI), healthy controls, and mice subjected to RCI.

“rs‐fMRI was acquired from patients with RCI (n = 43) and healthy controls (n = 30).”

43 RCI patients, 30 healthy controls, and varying numbers of mice per experimental group (typically n=6 to n=18).

“n = 43 patients, 30 controls.”

Clinical assessment was cross-sectional; animal studies assessed time points up to 8 weeks post-injury with peak effects at 4 weeks.

“In vivo local field potential recordings confirmed a reduction in PVN neuronal activity that peaked at four weeks post‐injury and recovered thereafter, paralleling the behavioral time course.”

RCI patients exhibit reduced hypothalamic spontaneous activity inversely correlated with anxiety severity.

“In patients with RCI, resting‐state fMRI (rs‐fMRI) revealed reduced hypothalamic spontaneous activity that was inversely correlated with anxiety severity.”

PVN oxytocinergic neurons are identified as a central node linking emotional regulation to bone-tendon interface repair via a sympathetic pathway.

“In mouse models, retrograde viral tracing and spatial transcriptomics identified PVNOXT neurons as the predominant labeled population within a polysynaptic PVN–IML–SCG sympathetic pathway connected to the subchondral bone region of the rotator cuff enthesis.”

Chemogenetic inhibition of PVN oxytocinergic neurons induced anxiety-like behaviors and impaired healing, while activation alleviated anxiety and enhanced recovery.

“Chemogenetic inhibition of PVNOXT neurons induced anxiety‐like behaviors and impaired BTI healing, whereas their activation alleviated anxiety and enhanced structural and biomechanical recovery.”

Clinical data are cross-sectional and cannot establish whether hypothalamic suppression precedes or follows anxiety onset.

“Because the clinical data are cross‐sectional, they cannot establish whether hypothalamic suppression precedes or follows anxiety onset.”