Psychological Stress Modulates Bone Remodeling Pathways in Normotensive and Hypertensive Rats: A Cellular and Molecular Approach

TL;DR

This study shows that psychological stress and hypertension together affect bone metabolism in rats, even before visible bone changes occur.

Contribution

The novel contribution is the demonstration of stress-induced early metabolic changes in bone remodeling in both normotensive and hypertensive rats.

Findings

Stress exposure reduced osteoblast activity and increased matrix remodeling enzymes.

TRAP-positive osteoclasts were observed only in stressed animals, indicating increased bone resorption.

Hypertensive rats showed higher baseline remodeling activity and a stronger response to chronic stress.

Abstract

Hypertension and
psychological stress are prevalent conditions
that may adversely affect bone health, yet their combined impact on
bone remodeling remains underexplored. This study aimed to investigate
the effects of acute and chronic stress on bone structure and remodeling
in normotensive and spontaneously hypertensive rats. Forty male rats
(20 normotensive Hannover and 20 spontaneously hypertensive) were
randomly assigned to control, acute stress, or chronic variable stress
groups. Acute stress consisted of a single 2 h restraint session,
while chronic variable stress involved five different stressors over
10 days. Bone remodeling was assessed using quantitative histology,
immunohistochemistry for VEGF, bone sialoprotein (BSP), osteocalcin
(OCN), and TRAP, as well as enzymatic activity analysis (MMP-2 and
MMP-9). Results: Neither acute nor chronic stress significantly altered
trabecular bone volume or collagen density within the study period.
However, stress exposure reduced osteoblast activity (OCN, BSP), increased
matrix remodeling enzymes (MMP-2, MMP-9), and promoted angiogenic
signaling (VEGF). Notably, TRAP-positive osteoclasts were observed
exclusively in stress-exposed animals, indicating elevated bone resorption.
Importantly, hypertensive rats exhibited inherently higher basal levels
of remodeling activity and MMP-2 expression compared to normotensive
controls, and showed a more pronounced response to chronic stress,
suggesting hypertension may predispose bone tissue to increased metabolic
vulnerability. According to the results of corticosterone dosage,
as well as histological and immunohistochemical analyses, it is provided
that stress promotes changes in bone metabolism, corroborating the
hypothesis that its effects occur early and precede detectable structural
modifications. These findings indicate that both hypertension and
psychological stress are relevant modulators of bone physiology, and
that their interaction may amplify metabolic changes in bone remodeling,
emphasizing the importance of monitoring bone health in hypertensive
individuals exposed to stress.

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