Chondrogenic differentiation of human subchondral progenitor cells is affected by synovial fluid from donors with osteoarthritis or rheumatoid arthritis

Abstract

BackgroundMicrofracture is a first-line treatment option for cartilage repair. In microfracture, subchondral mesenchymal cortico-spongious progenitor cells (CSP) enter the defect and form cartilage repair tissue. The aim of our study was to investigate the effects of joint disease conditions on the in vitro chondrogenesis of human CSP.MethodsCSP were harvested from the subchondral bone marrow. CSP characterization was performed by analysis of cell surface antigen pattern and by assessing the chondrogenic, osteogenic and adipogenic differentiation potential, histologically. To assess the effect of synovial fluid (SF) on chondrogenesis of CSP, micro-masses were stimulated with SF from healthy (ND), osteoarthritis (OA) and rheumatoid arthritis donors (RA) without transforming growth factor beta 3.ResultsCSP showed the typical cell surface antigen pattern known from mesenchymal stem cells and were capable of osteogenic, adipogenic and chondrogenic differentiation. In micro-masses stimulated with SF, histological staining as well as gene expression analysis of typical chondrogenic marker genes showed that SF from ND and OA induced the chondrogenic marker genes aggrecan, types II and IX collagen, cartilage oligomeric matrix protein (COMP) and link protein, compared to controls not treated with SF. In contrast, the supplementation with SF from RA donors decreased the expression of aggrecan, type II collagen, COMP and link protein, compared to CSP treated with SF from ND or OA.ConclusionThese results suggest that in RA, SF may impair cartilage repair by subchondral mesenchymal progenitor cells in microfracture, while in OA, SF may has no negative, but a delaying effect on the cartilage matrix formation.

Modulation of Synovial Fluid-Derived Mesenchymal Stem Cells by Intra-Articular and Intraosseous Platelet Rich Plasma Administration

“…While being promising, a limitation of our study is the considerable intersubject variability; therefore, a larger sample would possibly be necessary to draw more definitive conclusions. Our results encourage further studies in order to shed more light on the cellular and molecular mechanisms and to elucidate whether the PRP application in both modalities might lead to structural joint tissue changes as in vitro and preclinical researches using this therapy have reported [26, 39, 52]. Finally, further studies will be needed in order to increase our knowledge about SF as source of MSC and their therapeutic potential.…”

“…When fibrinolysis degrades this scaffold, growth factors within the fibrin scaffold such as IGF-I, HGF, PDGF, TGF- β 1, and platelet microparticles are released gradually. These growth factors have been proven to promote an anti-inflammatory macrophage phenotype [23, 34–36] and suppress the NF- κβ signaling pathway in synovial fibroblasts and chondrocytes of the superficial zone of AC [24] and induce the synthesis of hyaluronic acid and lubricin by synoviocytes and chondrocytes, respectively, with the latter preventing chondrocyte apoptosis, cartilage breakdown, and inhibition of the MSC release and migration [25, 37–39]. Although the decline of monocytes in the SF was not statistically significant, this fact together with all these modulatory and trophic effects of intra-articularly injected PRP on the SM, superficial AC, and SF could suggest a lower level of proinflammatory cytokines and restoration of the joint homeostasis leading to a more favorable SF environment for chondrogenic differentiation of MSCs [30, 37, 39, 40].…”

Inhibition of TAK1 and/or JAK Can Rescue Impaired Chondrogenic Differentiation of Human Mesenchymal Stem Cells in Osteoarthritis-Like Conditions

“…1,2 However, it should be noted that these studies were performed with differentiated cells rather than true progenitor cells. Krüger et al 3 showed that chondrogenic differentiation of human subchondral progenitor cells is affected by synovial fluid from donors with osteoarthritis (OA) or rheumatoid arthritis (RA). Previously, we have shown that factors secreted by the synovial membrane of OA joints inhibit chondrogenic differentiation of human mesenchymal stem cells (hMSCs), 4 thereby impairing successful tissue engineering.…”

Anatomically shaped tissue-engineered cartilage with tunable and inducible anticytokine delivery for biological joint resurfacing

“…There is growing evidence indicating that proinflammatory cytokines, and particularly IL-1, play an important role in the pathogenesis of OA (17)(18)(19), as well as the inhibition of mesenchymal stem cell (MSC)-based repair of cartilage (20)(21)(22)(23)(24)(25). However, natural inflammatory modulators such as IL-1 receptor antagonist (IL-1Ra) can inhibit IL-1 signaling (26), and studies have shown that biomaterial-mediated delivery of IL-1Ra can mitigate the degradative effects of IL-1 (27).…”