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Objective Osteoarthritis is not only characterized by cartilage degradation but also involves subchondral bone remodeling and osteophyte formation. Osteophytes are fibrocartilage-capped bony outgrowths originating from the periosteum. The pathophysiology of osteophyte formation is not completely understood. Yet, different research approaches are under way. Therefore, a histological osteophyte classification to achieve comparable results in osteophyte research was established for application to basic science research questions. Methods The osteophytes were collected from knee joints of osteoarthritis patients ( n = 10, 94 osteophytes in total) after joint replacement surgery. Their size and origin in the respective joint were photo-documented. To develop an osteophyte classification, serial tissue sections were evaluated using histological (hematoxylin and eosin, Masson's trichrome, toluidine blue) and immunohistochemical staining (collagen type II). Results Based on the histological and immunohistochemical evaluation, osteophytes were categorized into four different types depending on the degree of ossification and the percentage of mesenchymal connective tissue. Size and localization of osteophytes were independent from the histological stages. Conclusion This histological classification system of osteoarthritis osteophytes provides a helpful tool for analyzing and monitoring osteophyte development and for characterizing osteophyte types within a single human joint and may therefore contribute to achieve comparable results when analyzing histological findings in osteophytes.

Resume Objectif L’arthrose est non seulement caracterisee par une degradation du cartilage, mais comporte egalement un remodelage de l’os sous-chondral et la formation d’osteophytes. Les osteophytes sont des excroissances osseuses coiffees de fibrocartilage provenant du perioste. La physiopathologie de la formation d’osteophytes n’est pas completement comprise. Pourtant, differentes voies de recherche sont en cours. Par consequent, une classification histologique des osteophytes en vue d’obtenir des resultats comparables de la recherche sur les osteophytes a ete creee en vue d’une application aux questions de recherche fondamentale. Methodes Les osteophytes ont ete recueillis sur des genoux de patients souffrant d’arthrose ( n = 10 ; 94 osteophytes au total) apres mise en place d’une prothese. Leur taille et origine dans leur articulation respective furent documentees par photographies. Afin de developper une classification des osteophytes, des coupes seriees de tissus furent effectuees en utilisant des colorations histologiques (hematoxyline-eosine, trichrome de Masson, bleu de toluidine) et immunohistochimiques (collagene de type II). Resultats En fonction d’une evaluation histologique et immunohistochimique, les osteophytes furent classes en quatre types differents selon leur degre d’ossification et le pourcentage de tissu conjonctif mesenchymateux. La taille et la situation des osteophytes etaient independantes des stades histologiques. Conclusion Ce systeme de classification histologique des osteophytes arthrosiques fournit un outil utile pour l’analyse et le suivi du developpement des osteophytes et pour caracteriser le type d’osteophyte dans une seule articulation humaine. Il peut donc contribuer a obtenir des resultats comparables lors de l’analyse histologique des osteophytes.

Adipokines such as adiponectin and visfatin/pre-B-cell colony-enhancing factor (PBEF) have been recently shown to contribute to synovial inflammation in rheumatoid arthritis (RA). In this study, we evaluated the pathophysiological implication of visfatin/PBEF in the molecular patterns of RA synovial tissue, focusing on RA synovial fibroblasts (RASFs), key players in RA synovium. Expression of visfatin/PBEF in synovial fluid and tissue of RA patients was detected by immunoassays and immunohistochemistry. RASFs were stimulated with different concentrations of visfatin/PBEF over varying time intervals, and changes in gene expression were evaluated at the RNA and protein levels using Affymetrix array, real-time PCR, and immunoassays. The signaling pathways involved were identified. The influence of visfatin/PBEF on fibroblast motility and migration was analyzed. In RA synovium, visfatin/PBEF was predominantly expressed in the lining layer, lymphoid aggregates, and interstitial vessels. In RASFs, visfatin/PBEF induced high amounts of chemokines such as IL-8 and MCP-1, proinflammatory cytokines such as IL-6, and matrix metalloproteinases such as MMP-3. Phosphorylation of p38 MAPK was observed after visfatin/PBEF stimulation, and inhibition of p38 MAPK showed strong reduction of visfatin-induced effects. Directed as well as general fibroblast motility was increased by visfatin/PBEF-induced factors. The results of this study indicate that visfatin/PBEF is involved in synovial fibroblast activation by triggering fibroblast motility and promoting cytokine synthesis at central sites in RA synovium.

Introduction Chemerin stimulates migration of leukocytes to sites of inflammation and also increases inflammatory signaling in chondrocytes suggesting a function of chemerin in joint inflammation. Synovial fibroblasts (SF) are critically involved in synovitis and subsequent cartilage destruction. Here, we analyzed whether synovial fibroblasts express chemerin and its receptor CMKLR1. Further, the role of chemerin in synovial fibroblast chemotaxis, proliferation, insulin response and release of inflammatory proteins was studied. Methods Synovial tissue sections were labeled with chemerin antibody and chemerin was measured in synovial fluid by ELISA. Chemerin mRNA and protein as well as CMKLR1 expression were determined in SFs from patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Effects of chemerin on cytokines, chemokines and matrix metalloproteinases (MMP), and on proliferation, migration and insulin signaling were analyzed appropriately. Results SFs expressed CMKLR1 and chemerin mRNA, and chemerin protein was found in cell supernatants of synovial fibroblasts. Immunohistochemistry detected chemerin in synovial tissue predominantly localized within the lining layer. Chemerin was present in synovial fluids of RA, OA and psoriatic arthritis patients in similar concentrations. Chemerin neither increased IL-6 levels nor MMP-2 or − 9 activity in SFs. Also, it did not act as a chemoattractant for these cells. With respect to intracellular signaling, neither basal nor insulin-mediated phosphorylation of Akt was affected. However, chemerin significantly increased TLR4 mRNA and synthesis of CCL2 in SFs while CCL4 and − 5 were not altered. Cell proliferation of SFs, however, was modestly reduced by chemerin. Conclusions These data show that human SFs express both chemerin and its receptor. As chemerin enhanced expression of TLR4 and induced release of CCL2 in SFs, a role of this protein in innate immune system-associated joint inflammation is proposed.

s / Osteoarthritis and Cartilage 20 (2012) S54–S296 S115 214 EXPRESSION OF ADIPOCYTOKINES IN OSTEOARTHRITIS OSTEOPHYTES S. Junker , K.W. Frommer , G. Krumbholz , A. Lehr , S. Rehart , J. Steinmeyer , M. Rickert , G. Schett , U. Muller-Ladner , E. Neumann . 1 Internal Med. and Rheumatology Justus-Liebig-Univ. Giesen, Kerckhoff-Klinik, Bad Nauheim, Germany; Orthopedics and Trauma Surgery MarkusHosp., Frankfurt, Germany; 3 Experimental Orthopedics Univ. Hosp. Giesen and Marburg, Giesen, Germany; Orthopedics and Orthopedic Surgery Univ. Hosp. Giesen and Marburg, Giesen, Germany; 5 Internal Med. 3 Univ. of Erlangen-Nurnberg, Bad