Intestinal Sclerostin Deficiency Links Gut Dysbiosis to Altered Serotonin Homeostasis in Axial Spondyloarthritis.

ABSTRACT:

Background

Sclerostin regulates bone formation via Wnt/β-catenin signaling inhibition and contributes to intestinal epithelial homeostasis. Circulating sclerostin levels are reduced in axial spondyloarthritis (axSpA) and correlate with structural damage. LRP5, a receptor inhibited by sclerostin, also controls bone formation by regulating gut-derived serotonin synthesis, indicating a hormonal link between the intestine and bone. We hypothesized that gut dysbiosis-dependent downregulation of sclerostin alters intestinal serotonin production, contributing to disease-specific gut-bone signaling in axSpA.

Methods

We quantified sclerostin and the serotonin-synthesizing enzyme TPH1 by qRT-PCR, and assessed serotonin protein levels by immunohistochemistry in ileal biopsies from trea

SUBMITTER: Mauro D 

PROVIDER: S-EPMC12858532 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature