Rheumatoid Arthritis in the View of Osteoimmunology.

Mélanie Auréal,Fabienne Coury,Irma Machuca-Gayet

doi:10.3390/biom11010048

Mélanie Auréal, Fabienne Coury + Show 1 more

Open Access

https://doi.org/10.3390/biom11010048

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Abstract

Rheumatoid arthritis is characterized by synovial inflammation and irreversible bone erosions, both highlighting the immense reciprocal relationship between the immune and bone systems, designed osteoimmunology two decades ago. Osteoclast-mediated resorption at the interface between synovium and bone is responsible for the articular bone erosions. The main triggers of this local bone resorption are autoantibodies directed against citrullinated proteins, as well as pro-inflammatory cytokines and the receptor activator of nuclear factor-κB ligand, that regulate both the formation and activity of the osteoclast, as well as immune cell functions. In addition, local bone loss is due to the suppression of osteoblast-mediated bone formation and repair by inflammatory cytokines. Similarly, inflammation affects systemic bone remodeling in rheumatoid arthritis with the net increase in bone resorption, leading to systemic osteoporosis. This review summarizes the substantial progress that has been made in understanding the pathophysiology of systemic and local bone loss in rheumatoid arthritis.

Highlights

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that primarily causes tenderness, swelling, and destruction in joints with the resulting disability
B; osteoclastassociated receptor (OSCAR): Osteoclast associated receptor; PLCγ: Phospholipase C gamma; RANK: Receptor activator of nuclear factor kappa B; RANKL: RANK ligand; Syk: Spleen tyrosine kinase; TNF: Tumor necrosis factor; TNF receptor-associated factor-6 (TRAF6): TNF receptor-associated factor 6; TREM-2: Triggering receptor expressed on myeloid cell
Due to the fact that chronic inflammation is considered as the primary trigger for bone damage, the discovery of systemic bone loss and bone erosion in healthy ACPApositive individuals suggests that bone loss and bone resorption precede the clinical onset of inflammation and may be caused by inflammation, absent during the preclinical phases of RA, and by autoantibodies such as anti-citrullinated peptide antibodies (ACPAs), present long before arthritis [7,83,84,85]

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder that primarily causes tenderness, swelling, and destruction in joints with the resulting disability. While its precise etiology is unknown, RA is considered to develop as a result of interactions between inherited genetic factors and environmental triggers during pre-clinical phases of the disease, in which tolerance is broken and autoantibodies, including anti-citrullinated peptide antibodies (ACPAs), are produced long before the appearance of the first joint symptoms. RA is characterized by dysregulated inflammatory and immune processes in the synovium of the joints as well as bone loss, highlighting this disease as an excellent model for gaining insights into osteoimmunology.

Bone Loss in RA

Osteoclasts Mediate Bone Destruction in RA

Osteoclast Differentiation in RA

Innate Immune Mechanisms

T-Cells

Pro-Inflammatory Cytokines

Autoimmunity

MicroRNAs

Autophagy

Inhibition of Osteoformation in RA

Findings

Conclusions