Extracellular ERp57 promotes fibronectin fibril formation during matrix assembly of articular cartilage.

ABSTRACT: Fibronectin 1 (FN1), a general organizer of extracellular matrix (ECM) in various connective tissues, contains disulfide bridges formed by protein disulfide isomerases (PDIs). ERp57 (PDIA3), an ER resident glycoprotein-specific PDI, is also detectable in cartilage extracellular matrix (ECM). Here, we analyzed the extracellular role of ERp57 in FN1 fibrillogenesis in cartilage. ERp57 KO mice exhibited reduced ECM density. Isolated chondrocytes thereof and C28/I2 ERp57 KO chondrocytes formed fewer and shorter FN1 fibrils than WT cells. Significantly, cell membrane-impermeable thiol blockers reduced FN1 assembly in WT cells, while active recombinant ERp57 protein increased it only in the absence of thiol blockers, emphasizing the necessity of ERp57-mediated disulfide bridge formation for FN1

SUBMITTER: Rellmann Y 

PROVIDER: S-EPMC12702194 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature