Session Title: Cytokines, Mediators, and Gene Regulation
Session Type: Abstract Submissions (ACR)
Obesity is an established risk factor in osteoarthritis (OA), but there is not much known about the interaction between bone formation and the so-called adipo(cyto)kines. Adipokines, such as adiponectin (Ad), visfatin (Vis) or resistin (Res), are adipose tissue-derived factors, which are associated with the pathogenesis of rheumatoid arthritis (RA) and OA. Adipokines can be produced by other cell types, e.g. fibroblasts, osteoblasts, osteoclasts and chondrocytes. However, in contrast to their joint-destructive effects in RA, their role in joint remodeling in OA, specifically in osteophyte formation, is still unclear. Therefore, the expression of adipokines in osteophyte development and cells of bone formation and their effect on these cells were analyzed.
Osteophytes, cartilage and osteoblasts were obtained from OA patients during joint replacement surgery. Serial sections of bone tissue were stained (Masson trichrome, TRAP) and scored from grade one (no ossification, mainly connective tissue and cartilage) to five (ossified, mineralized osteophyte, <10% connective tissue). For analysis of adipokine localization, immunohistochemistry was performed to detect alkaline phosphatase, collagen-type II, Ad, Vis, and Res. Immunoassays for Vis were performed on cartilage and isolated primary chondrocyte lysates. Osteoblast cultures were stimulated with Ad or Res and measurements of IL-6, IL-8, and MCP-1 were performed in cell culture supernatants.
Ad, Res and Vis were detectable in all osteophyte grades. In osteophytes without ossification (grade 1), especially Ad and, to a lower extent, Res and Vis were localized in connective tissue fibroblasts. In ossified osteophytes (grade 2-5), Res and Vis protein expression was co-localized with osteoclasts and osteoblasts. Vis was detectable additionally in chondrocytes in osteophytes of all grades (50 % stained chondrocytes). Vis expression in human cartilage and cultured chondrocytes was confirmed on protein and mRNA level. Ad was detectable in co-localization with osteoblasts as well as around blood vessels.
Vis expression in osteoblasts was confirmed on mRNA level. Immunocytochemistry on cultured osteoblasts confirmed the expression of Ad, Res and Vis. Stimulation of osteoblasts with Ad and Res led to an increased IL-6, IL-8 and MCP-1 release when compared to unstimulated controls (Ad: 5,7-fold, 9,5-fold, 3,6-fold, respectively / Res: 1,7-fold, 1,6-fold, 1,3-fold, respectively). The immunomodulatory effect of Ad on osteoblasts was stronger than the effect of Res.
The expression of Ad and Vis in osteophyte connective tissue and cartilage suggests an involvement in early osteophyte formation. Res and Vis expression by osteoblasts and osteoclasts in ossified osteophytes suggests a role in bone remodeling of osteophytes at later stages. Osteoblasts respond to the stimulation with Ad and Res with an increased secretion of inflammatory mediators. Therefore, adipokines are most likely involved in osteophyte formation at different stages of OA and affect different cell types of cartilage and bone formation.
Acknowledgement: Funded by the ANCYLOSS project of the German Ministry of Research and Education (BMBF).
G. A. Schett,
« Back to 2012 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-role-of-adipocytokines-in-osteophyte-formation-in-osteoarthritis/