Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis

Abstract

BackgroundMultinucleated giant cells have been noticed in diverse arthritic conditions since their first description in rheumatoid synovium. However, their role in the pathogenesis of osteoarthritis (OA) or rheumatoid arthritis (RA) still remains broadly unknown. We aimed to study the presence and characteristics of multinucleated giant cells (MGC) both in synovium and in subchondral bone tissues of patients with OA or RA.MethodsKnee synovial and subchondral bone samples were from age-matched patients undergoing total joint replacement for OA or RA, or non-arthritic post mortem (PM) controls. OA synovium was stratified by histological inflammation grade using index tissue sections. Synovitis was assessed by Krenn score. Histological studies employed specific antibodies against macrophage markers or cathepsin K, or TRAP enzymatic assay.ResultsInflamed OA and RA synovia displayed more multinucleated giant cells than did non-inflamed OA and PM synovia. There was a significant association between MGC numbers and synovitis severity. A TRAP negative/cathepsin K negative Langhans-like subtype was predominant in OA, whereas both Langhans-like and TRAP-positive/cathepsin K-negative foreign-body-like subtypes were most commonly detected in RA. Plasma-like and foam-like subtypes also were observed in OA and RA synovia, and the latter was found surrounding adipocytes. TRAP positive/cathepsin K positive osteoclasts were only identified adjacent to subchondral bone surfaces. TRAP positive osteoclasts were significantly increased in subchondral bone in OA and RA compared to PM controls.ConclusionsMultinucleated giant cells are associated with synovitis severity, and subchondral osteoclast numbers are increased in OA, as well as in RA. Further research targeting multinucleated giant cells is warranted to elucidate their contributions to the symptoms and joint damage associated with arthritis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0664-5) contains supplementary material, which is available to authorized users.

Circulating T helper 9 cells and increased serum interleukin‐9 levels in patients with knee osteoarthritis

“…Subchondral inflammation might also contribute to increased bone turnover and joint damage in both OA and RA . Although OA and RA have differences in their etiologies, with mechanical factors being key to knee OA progression and specific immunity driving RA, common mechanisms may contribute to joint damage and pain in both conditions . However, the different mechanisms and the specific roles of Th9 and IL9 in autoimmune diseases and OA require further study.…”

Associations of Symptomatic Knee Osteoarthritis With Histopathologic Features in Subchondral Bone

“…In human OA, NGF is up‐regulated in synovium and subchondral bone , and increased synovial NGF expression was associated with symptomatic knee OA , although the relevance of subchondral NGF expression has not been clarified. Increased density of tartrate‐resistant acid phosphatase (TRAP)–positive osteoclasts in subchondral bone has also been shown to be associated with OA and knee symptoms . Inflammatory CD68‐positive macrophages were also detected in subchondral bone marrow compartments in human OA .…”

MRI of synovitis and joint fluid

“…The synovium in OA is histologically characterized by thickening, hyperplasia, fibrosis, and stromal vascularization . With immune activation, there is an influx of predominantly macrophages and T‐cell lymphocytes, from the vascular compartment in response to cytokines and cell adhesion molecules, with other contributing cells including synoviocytes and chondrocytes .…”

“…10 The synovium in OA is histologically characterized by thickening, hyperplasia, fibrosis, and stromal vascularization. 11 With immune activation, there is an influx of predominantly macrophages and T-cell lymphocytes, from the vascular compartment in response to cytokines and cell adhesion molecules, 12,13 with other contributing cells including synoviocytes and chondrocytes. 14 Degradation of hyaline cartilage, subchondral bone, and other articular structures results in the release of inflammatory molecules, further promoting synovial inflammation.…”