The online version of this article (doi:10.1186/s12891-015-0664-5) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
IP-P conceived of the study, participated in its design, acquisition of data, performed statistical analysis and interpretation of data, and drafted the manuscript. RL and JAR-B participated in the interpretation of data and helped to draft the manuscript. GH-B conceived of the study and design, and helped to draft the manuscript. DAW conceived of the study, design and coordination, interpretation of data and helped to draft the manuscript. All authors read and approved the final manuscript.
Multinucleated 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.
Knee 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.
Inflamed 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.
Multinucleated 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.
Additional file 1: Morphological MGC foam subtype and CD68 positive cells surrounding fat cells in OA and in RA. A and B. MGCs displaying a foam-like subtype were identified near to and surrounding fat cells in inflamed synovia from patients with either OA (A) or RA (B). Haematoxylin and eosin staining. Scale bar = 20 μm. Open arrows indicate foam-like MGC and A = adipocyte. C and D. Multiple mononuclear CD68 positive cells were found in a crown-like structure encircling adipocyte cells in both OA (C) and RA (D). Immunohistochemistry for CD68, using eosin contrast. Scale bar = 100 μm. (TIFF 3238 kb)12891_2015_664_MOESM1_ESM.tiff
Stoppiello LA, Mapp PI, Wilson D, Scammell BE, Orth F, Walsh DA. Structural associations of symptomatic knee osteoarthritis. Arthritis Rheum. 2014;66:3018–27. CrossRef
Walsh DA, McWilliams DF, Turley MJ, Dixon MR, Fransès RE, Mapp PI, et al. Angiogenesis and nerve growth factor at the osteochondral junction in rheumatoid arthritis and osteoarthritis. Rheumatology (Oxford). 2010;49:1852–61. CrossRef
Gómez-Mateo MDC, Monteagudo C. Nonepithelial skin tumors with multinucleated giant cells. Semin Diagn Pathol. 2013;30:58–72. CrossRef
Bucklandwright C. Subchondral bone changes in hand and knee osteoarthritis detected by radiography. Osteoarthr Cartil. 2004;12:10–9. CrossRef
Sagar DR, Ashraf S, Xu L, Burston JJ, Menhinick MR, Poulter CL, Bennett AJ, Walsh DA, Chapman V: Osteoprotegerin reduces the development of pain behaviour and joint pathology in a model of osteoarthritis. Ann rheum Dis 2013 [Epub ahead of print].
Fransen J, van Riel PLCM. The Disease Activity Score and the EULAR response criteria. Clin Exp Rheumatol. 2005;23(5 Suppl 39):S93–9. PubMed
Park JK, Rosen A, Saffitz JE, Asimaki A, Litovsky SH, Mackey-Bojack SM, et al. Expression of cathepsin K and tartrate-resistant acid phosphatase is not confined to osteoclasts but is a general feature of multinucleated giant cells: systematic analysis. Rheumatology (Oxford). 2013;52:1529–33. CrossRef
Gómez R, Villalvilla A, Largo R, Gualillo O, Herrero-Beaumont G: TLR4 signalling in osteoarthritis-finding targets for candidate DMOADs. Nat Rev Rheumatol 2015;11(3):159-70.
Ferraz-Amaro I, González-Juanatey C, López-Mejias R, Riancho-Zarrabeitia L, González-Gay MA. Metabolic syndrome in rheumatoid arthritis. Mediators Inflamm. 2013;2013:11. CrossRef
Jösten M, Rudolph R. Methods for the differentiation of giant cells in canine and feline neoplasias in paraffin sections. Zentralbl Vet A. 1997;44:630. CrossRef
Nordborg E, Bengtsson B, Petursdottir V, Nordborg C. Morphological aspects of giant cells in giant cell arteritis: an electron-microscopic and immunocytochemical study. Clin Exp Rheumatol. 1997;15:129–34. PubMed
- Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis
Jorge A Roman-Blas
David A Walsh
- BioMed Central
Neu im Fachgebiet Orthopädie und Unfallchirurgie
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