Tcirg1 deficiency delays osteoarthritis progression by impairing lysosome acidification and peripheral accumulation in osteoclasts.

ABSTRACT:

Introduction

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by articular cartilage loss and aberrant subchondral bone remodeling. "T-cell immune regulator 1" (Tcirg1), which encodes the a3 subunit of the V-ATPase, has been demonstrated to inhibit the formation of large osteoclasts by reducing intracellular calcium oscillations. Mutations in the Tcirg1 gene sequence have been associated with osteopetrosis by impairing lysosomal transport in osteoclasts. This study aims to assess the impact of Tcirg1 on OA progression and to explore its therapeutic potential for the disease treatment.

Methods

Proteomic comparison of weight-bearing region (WBR) versus non-weight-bearing region (NWBR) of the subchondral bone was performed in

SUBMITTER: Sun R 

PROVIDER: S-EPMC12454451 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature