Interaction between Synovial Inflammatory Tissue and Bone Marrow in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) leads to destruction of cartilage and bone. Whether rheumatoid arthritis also affects the adjacent bone marrow is less clear. In this study, we investigated subcortical bone marrow changes in joints from patients with RA. We describe penetration of the cortical barrier by synovial inflammatory tissue, invasion into the bone marrow cavity and formation of mononuclear cell aggregates with B cells as the predominant cell phenotype. B cells expressed common B cell markers, such as CD20, CD45RA, and CD79a, and were mature B cells, as indicated by CD27 expression. Plasma cells were also present and were enriched in the regions between aggregates and inflammatory tissue. Moreover, molecules for B cell chemoattraction, such as BCA-1 and CCL-21, homing, mucosal addressin cell adhesion molecule-1 and survival, BAFF, were expressed. Endosteal bone next to subcortical bone marrow aggregates showed an accumulation of osteoblasts and osteoid deposition. In summary, we show that synovial inflammatory tissue can reach the adjacent bone marrow by fully breaking the cortical barrier, which results in formation of B cell-rich aggregates as well as increased formation of new bone. This suggests that bone marrow is an additional compartment in the disease process of RA.

How antirheumatic drugs protect joints from damage in rheumatoid arthritis

“…CD20-positive B cell aggregates are also found in the juxtaarticular bone marrow of RA patients (17). These aggregates are associated with endosteal bone formation and accumulation of osteoblasts at endosteal sites, suggesting that B cells may stimulate endosteal bone formation.…”

“…This localization is very close to mineralized cartilage, the initial location of the invasion, which then continues to the subchondral bone underneath. Upon growth of these lesions and by using cortical bone channels, inflammatory synovial tissue finally reaches the bone marrow cavity and leads to an inflammation therein, which consists of lymphocytic aggregates dominated by mature B cells (17)(18)(19). Moreover, primary inflammatory lesions in the bone marrow may use these cortical bone channels, which span between the bone marrow and the joint cavity, to fuel synovial inflammation (20,21).…”

Tenosynovitis and osteoclast formation as the initial preclinical changes in a murine model of inflammatory arthritis

“…In these contact regions, the first osteoclasts appear and start to resorb subchondral bone and mineralized cartilage (10,23). Thus, even before the onset of synovial inflammation, osteoclasts start their destructive work and pave the way for early B cell accumulation in the adjacent bone marrow, which is closely linked to breaking of the cortical bone barrier (24,25). Since osteoclasts appear even before the first clinical signs of arthritis, destructive changes begin to occur even before arthritis is clinically apparent in the patients.…”

Cytokines in Rheumatoid Arthritis (RA)

“…This step is the starting point of the cytokine efect, which augments the inlammation and stimulate the other systems (such as lipid mediators, nitric oxide, RANKL-RANK signaling, etc.) that cause joint destruction and the organ damage [11][12][13].…”

“…Most are pro-inlammatory cytokines. They cause mostly local joint destruction and also systemic efects of the disease and include IL-1, TNF-alpha, IL-6, IL-15, IL-16, IL-17, IL-18, interferon (IFN)-γ, granulocyte macrophage-colony stimulating factor) [10][11][12].…”