The Role of Synovial Macrophages and Macrophage-Produced Mediators in Driving Inflammatory and Destructive Responses in Osteoarthritis

Bondeson, Jan; Wainwright, S.D.; Hughes, Clare Elizabeth; Caterso, Bruce

doi:10.5772/28284

Cited by 66 publications

(108 citation statements)

References 42 publications

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“…Interleukins (IL-1 and IL-6) and TNFproinflammatory cytokines, are directly associated with pain (Svensson 2010), which may result from synovial macrophages. These cytokines incite chondrocytes to generate inflammatory mediators such as prostaglandin E2, superoxide, nitric oxide, proteolytic enzymes [disintegrin, metalloproteinase domains with thrombospondin motifs (ADAMTS) and MMPs] (Rutgers et al 2009;Bondeson et al 2010). However, studies have found no significant difference in the amount of PG E2 present in the synovial fluid (SF) of untreated horses or horses treated for lameness with intra-articular anesthetics.…”

Section: Origin Of Painmentioning

confidence: 93%

Osteoarthritis in horses - Part 1: relationship between clinical and radiographic examination for the diagnosis

Souza

2016

Braz. arch. biol. technol.

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Section: Origin Of Painmentioning

confidence: 93%

Osteoarthritis in horses - Part 1: relationship between clinical and radiographic examination for the diagnosis

Souza

2016

Braz. arch. biol. technol.

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“…The increased IL-1b protein production by AMs in the coculture group is potentially significant due to the known involvement of IL-1b in promoting inflammation in OA. 6 Similarly, the increase in VEGF protein is potentially significant because it has been previously been shown to be enhanced in OA, 83 with angiogenesis tightly linked to inflammation. 84 OA progression represents a complex set of processes that are mediated by a number of factors.…”

Section: Discussionmentioning

confidence: 99%

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Samavedi

Díaz‐Rodríguez

Erndt-Marino

et al. 2017

Tissue Engineering Part A

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The goal of the present study was to develop a fully three-dimensional (3D) coculture system that would allow for systematic evaluation of the interplay between activated macrophages (AMs) and chondrocytes in osteoarthritic disease progression and treatment. Toward this end, our coculture system was first validated against existing in vitro osteoarthritis models, which have generally cultured healthy normal chondrocytes (NCs)-in two-dimensional (2D) or 3D-with proinflammatory AMs in 2D. In this work, NCs and AMs were both encapsulated within poly(ethylene glycol) diacrylate hydrogels to mimic the native 3D environments of both cell types within the osteoarthritic joint. As with previous studies, increases in matrix metalloproteinases (MMPs) and proinflammatory cytokines associated with the early stages of osteoarthritis were observed during NC-AM coculture, as were decreases in protein-level Aggrecan and collagen II. Thereafter, the coculture system was extended to osteoarthritic chondrocytes (OACs) and AMs to evaluate the potential effects of AMs on pre-existing osteoarthritic phenotypes. OACs in coculture with AMs expressed significantly higher levels of MMP-1, MMP-3, MMP-9, MMP-13, IL-1b, TNF-a, IL-6, IL-8, and IFN-g compared to OACs in mono-culture, indicating that proinflammatory macrophages may intensify the abnormal matrix degradation and cytokine secretion already associated with OACs. Likewise, AMs cocultured with OACs expressed significantly more IL-1b and VEGF-A compared to AM mono-culture controls, suggesting that OACs may intensify abnormal macrophage activation. Finally, OACs cultured in the presence of nonactivated macrophages produced lower levels of MMP-9 and proinflammatory cytokines IL-1b, TNF-a, and IFN-g compared to OACs in the OAC-AM system, results that are consistent with anti-inflammatory agents temporarily reducing certain OA symptoms. In summary, the 3D coculture system developed herein captures several key features of inflammatory OA and may prove useful in future screening of therapeutic agents and/or assessment of disease progression mechanisms.

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“…Bondeson et al reported that depletion of CD14 + synovial macrophages results in decline of IL-1b and TNF-a, which may in turn inhibit the release of IL-6, chemokines, and MMPs in OA synovial cells. 15 This would indicate that CD14 plays a role in inflammatory and destructive responses from the synovial fibroblasts. Soluble CD14 is increased in synovial fluid in both early and advanced stages of human knee OA, and the synovial fluid of early OA patients has been shown to modulate inflammatory responses of synoviocytes to TLR2 and TLR4 ligands through soluble CD14.…”

Section: Cd14 and Proinflammatory Cytokines On Chondrogenesis In Oa Smentioning

confidence: 99%

“…13,15,16,30 For cell sorting, an MSCS method (Miltenyi Biotec, Auburn, CA) was used. Briefly, isolated cells were counted and suspended at a concentration of 10 7 cells per 100 mL of FCM buffer, followed by incubation with primary antibodies at 4°C for 20 min.…”

Section: Magnetic-activated Cell Sortingmentioning

confidence: 99%

Effects of CD14 Macrophages and Proinflammatory Cytokines on Chondrogenesis in Osteoarthritic Synovium-Derived Stem Cells

Sun

Lee

Seong

et al. 2014

Tissue Engineering Part A

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We investigated the effects of CD14 macrophages and proinflammatory cytokines on chondrogenic differentiation of osteoarthritic synovium-derived stem cells (SDSCs). Osteoarthritic synovial fluid was analyzed for interleukin-1b (IL-1b), tumor necrosis factor-a (TNF-a), and IL-6. Levels of stem cell surface markers in osteoarthritic SDSCs were evaluated using flow cytometry. CD14-negative cells were obtained using magnetically activated cell sorting. We compared chondrogenic potentials between whole cells and CD14-negative cells in CD14 low cells and CD14 high cells, respectively. To assess whether nuclear factor-kB (NF-kB) and CCAAT/enhancer-binding protein b (C/EBPb) modulate IL-1b-induced alterations in chondrogenic potential, we performed small interfering RNA transfection. We observed a significant correlation between the CD14 ratio in osteoarthritic SDSCs and IL-1b and TNF-a in osteoarthritic synovial fluid. Phenotypic characterization of whole cells and CD14-negative cells showed no significant differences in levels of stem cell markers. mRNA expression of type II collagen was higher in CD14-negative cell pellets than in whole cell pellets. Immunohistochemical staining indicated higher levels of type II collagen in the CD14-negative cell pellets of CD14 high cells than in whole cell pellets of CD14 high cells. As expected, IL-1b and TNF-a significantly inhibited the expression of chondrogenic-related genes in SDSCs, an effect which was antagonized by knockdown of NF-kB and C/EBPb. Our results suggest that depletion of CD14 + synovial macrophages leads to improved chondrogenic potential in CD14 high cell populations in osteoarthritic SDSCs, and that NF-kB (RelA) and C/EBPb are critical factors mediating IL-1b-induced suppression of the chondrogenic potential of human SDSCs.

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The Role of Synovial Macrophages and Macrophage-Produced Mediators in Driving Inflammatory and Destructive Responses in Osteoarthritis

Cited by 66 publications

References 42 publications

Osteoarthritis in horses - Part 1: relationship between clinical and radiographic examination for the diagnosis

Osteoarthritis in horses - Part 1: relationship between clinical and radiographic examination for the diagnosis

A Three-Dimensional Chondrocyte-Macrophage Coculture System to Probe Inflammation in Experimental Osteoarthritis

Effects of CD14 Macrophages and Proinflammatory Cytokines on Chondrogenesis in Osteoarthritic Synovium-Derived Stem Cells

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