Targeting chondrocytes for arresting bony fusion in ankylosing spondylitis.

ABSTRACT: Bony fusion caused by pathological new bone formation manifests the clinical feature of ankylosing spondylitis (AS). However, the underlying mechanism remains elusive. Here we discovered spontaneous kyphosis, arthritis and bony fusion in mature CD4-Cre;Ptpn11^f/f mice, which present the pathophysiological features of AS. A population of CD4-Cre-expressing proliferating chondrocytes was SHP2 deficient, which could differentiate into pre-hypertrophic and hypertrophic chondrocytes. Functionally, SHP2 deficiency in chondrocytes impeded the fusion of epiphyseal plate and promoted chondrogenesis in joint cavity and enthesis. Mechanistically, aberrant chondrocytes promoted ectopic new bone formation through BMP6/pSmad1/5 signaling. It is worth emphasizing that such pathological thicknes

SUBMITTER: Shao F 

PROVIDER: S-EPMC8585952 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature