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

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.