Hypertension fuels osteoarthritis through neuroendocrine signaling.

This study identifies a neuroendocrine pathway where hypertension may accelerate osteoarthritis through vasopressin signaling, but further research is needed to understand its clinical relevance.

Summary and findings

This study investigated the role of vasopressin receptor signaling in osteoarthritis (OA) exacerbated by hypertension. It utilized nationwide cohort analyses and hypertensive mouse models to explore the relationship between elevated blood pressure and OA progression. The findings suggest a neuroendocrine pathway linking hypertension to OA pathogenesis.

Abstract

Osteoarthritis (OA) is a degenerative joint disease, the progression of which is accelerated by systemic metabolic stress. Here, we identified a neuroendocrine pathway through which hypertension accelerates OA pathogenesis in joints predisposed by mechanical injury or aging. Nationwide cohort analyses and hypertensive mouse models demonstrated that elevated blood pressure exacerbates OA pathogenesis. OA-primed chondrocytes up-regulated arginine vasopressin (AVP) receptor 1A (AVPR1A), rendering them responsive to hypertension-associated circulating AVP. AVP-AVPR1A signaling enhanced catabolic signaling while suppressing anabolic regulators, thereby promoting cartilage catabolism. Genetic deletion or pharmacological inhibition of AVPR1A protected against hypertension-driven OA acceleration. Transcriptomic profiling and gene-silencing analyses identified NR4A3 as the principal downstream transcriptional mediator. Collectively, these findings establish the AVP-AVPR1A axis as a mechanistic link between systemic hypertensive stress and joint degeneration.

Limitations

Not reported in abstract.

Elsewhere in the Vasopressin corpus