Cytokine profiles in the joint depend on pathology, but are different between synovial fluid, cartilage tissue and cultured chondrocytes

Abstract

IntroductionThis study aimed to evaluate whether profiles of several soluble mediators in synovial fluid and cartilage tissue are pathology-dependent and how their production is related to in vitro tissue formation by chondrocytes from diseased and healthy tissue.MethodsSamples were obtained from donors without joint pathology (n = 39), with focal defects (n = 65) and osteoarthritis (n = 61). A multiplex bead assay (Luminex) was performed measuring up to 21 cytokines: Interleukin (IL)-1α, IL-1β, IL-1RA, IL-4, IL-6, IL-6Rα, IL-7, IL-8, IL-10, IL-13, tumor necrosis factor (TNF)α, Interferon (IFN)γ, oncostatin M (OSM), leukemia inhibitory factor (LIF), adiponectin, leptin, monocyte chemotactic factor (MCP)1, RANTES, basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), vascular growth factor (VEGF).ResultsIn synovial fluid of patients with cartilage pathology, IL-6, IL-13, IFNγ and OSM levels were higher than in donors without joint pathology (P ≤0.001). IL-13, IFNγ and OSM were also different between donors with cartilage defects and OA (P <0.05). In cartilage tissue from debrided defects, VEGF was higher than in non-pathological or osteoarthritic joints (P ≤0.001). IL-1α, IL-6, TNFα and OSM concentrations (in ng/ml) were markedly higher in cartilage tissue than in synovial fluid (P <0.01). Culture of chondrocytes generally led to a massive induction of most cytokines (P <0.001). Although the release of inflammatory cytokines was also here dependent on the pathological condition (P <0.001) the actual profiles were different from tissue or synovial fluid and between non-expanded and expanded chondrocytes. Cartilage formation was lower by healthy unexpanded chondrocytes than by osteoarthritic or defect chondrocytes.ConclusionsSeveral pro-inflammatory, pro-angiogenic and pro-repair cytokines were elevated in joints with symptomatic cartilage defects and/or osteoarthritis, although different cytokines were elevated in synovial fluid compared to tissue or cells. Hence a clear molecular profile was evident dependent on disease status of the joint, which however changed in composition depending on the biological sample analysed. These alterations did not affect in vitro tissue formation with these chondrocytes, as this was at least as effective or even better compared to healthy chondrocytes.

Ageing and the pathogenesis of osteoarthritis

“…Indeed, the SASP seems to be regulated independently from cell cycle arrest 39,40 . Some of the most highly upregulated SASP-related factors, such as IL-1α, IL-6 and monocyte chemoattractant protein 1 (MCP-1, also known as CC chemokine ligand 2 (CCL2)) are found in OA cartilage 41 , hindering efforts to determine whether the level of a particular mediator is due to senescence or a result of OA. The cell type responsible for producing these cytokines is also difficult to determine.…”

Dexamethasone Release from Within Engineered Cartilage as a Chondroprotective Strategy Against Interleukin-1α

“…At 1 week, while reduced, these cytokines remained elevated above chronic levels. Tsuchida et al analyzed the synovial cytokine profiles of patients undergoing microfracture or autologous cell implantation (ACI) for focal defect repair 20 and observed increased concentrations of inflammatory cytokines in the synovial fluid of injured as compared with healthy joints. The increased presence of cytokines in injured joints may contribute to the inferior clinical results observed for ACI in some patients, [21][22][23][24] as elevated levels of inflammatory mediators have previously been shown to hamper cartilage regeneration.…”

Expression of the calcium-sensing receptor in monocytes from synovial fluid is increased in osteoarthritis

“…Thus, CaSR signalling is ligand-dependent and depends in some extent to the cell-type in which it is studied [1]. It is well known that a broad range of cytokines can be found in the synovial fluid of OA patients, even if it is at a lesser degree than in RA [24][25][26][27]. Thus, one may hypothesise that these cytokines could influence CaSR expression in synovial fluid monocytes, as it has been shown in other cellular models [10,[20][21][22].…”