Abstract :
[en] Osteoarthritis (OA) is no longer regarded as a simple “wear-and-tear” degenerative disease of the cartilage, but rather as a whole-joint disease affecting all components of the joint, including cartilage, synovium, fat pad, subchondral bone, menisci and ligaments [1]. OA is a widespread joint disease among people, especially over the age of 65, and is a leading cause of joint pain, stiffness, and disability. Traditionally considered a degenerative disease driven by mechanical loading [2], obesity [3], or axial disorders [4], OA is now recognized as a multifactorial condition closely associated with components of the metabolic syndrome [5,6] , including dyslipidemia [7] and insulin resistance. These metabolic alterations, together with inflammatory stimuli [cytokines or Damage-Associated Molecular Patterns (DAMPs)] [8], structural factors (age-related changes) [9], and other mechanical events (trauma, cartilage breakdown products, bone marrow lesions) [5], contribute to OA pathogenesis. Although OA has long been regarded as a non-inflammatory disease of the cartilage, the synovium also displays clear inflammatory features [1,8,10]. The synovial membrane is a connective tissue lining the joint cavity. It plays a crucial role in maintaining joint homeostasis and lubrication, and consists of two layers: the lining and the sublining. Several studies have demonstrated an association between endoplasmic reticulum (ER) stress and synovitis [11,12]. In our laboratory, we have previously identified by mass spectrometry 11 chaperone proteins of the ER stress (BiP, HYOU1, MANF, PDIA4, GANAB, HSP90B1, TXNDC5, DNAJB11, LMAN1, ERP29, and CALR), whose expression levels correlated with a histological inflammatory score established on synovial membranes obtained from patients with inflammatory joint diseases. These biopsies were obtained from patients with OA, chronic pyrophosphate disease (CPPD) or rheumatoid arthritis (RA), and exhibited a continuous degree of inflammation [13]. The ER is an intracellular organelle essential for proper protein folding and trafficking via chaperone proteins. Beyond their classic role in protein folding, several ER chaperones can also influence cell survival by enhancing inflammation and immunogenicity during pathological ER stress. Therefore, our study aims to investigate the impact of these 11 ER stress proteins on the initiation of fibrosis in arthritic diseases, with a particular focus on OA.
