Guiding synovial inflammation by macrophage phenotype modulation: an in vitro study towards a therapy for osteoarthritis

Utomo, Lizette; Osch, Gerjo J. V. M. van; Bayon, Yves; Verhaar, Jan A N; Bastiaansen-Jenniskens, Y.M.

doi:10.1016/j.joca.2016.04.013

Cited by 59 publications

(66 citation statements)

References 49 publications

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“…Macrophages are accumulated and polarised (M1 or M2) in the synovium and articular cavity during OA development, suggesting a correlation between macrophages and OA 25. A recent in vitro study by Utomo et al revealed that M1 but not M2 macrophages exert prominent effects on inflammation and degeneration of cultured cartilage explants 39. Furthermore, systemic depletion of macrophages reduces osteophyte formation in a collagen-induced arthritis model 40.…”

Section: Discussionmentioning

confidence: 99%

Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2

et al. 2018

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ObjectivesTo investigate the roles and regulatory mechanisms of synovial macrophages and their polarisation in the development of osteoarthritis (OA).MethodsSynovial tissues from normal patients and patients with OA were collected. M1 or M2-polarised macrophages in synovial tissues of patients with OA and OA mice were analysed by immunofluorescence and immunohistochemical staining. Mice with tuberous sclerosis complex 1 (TSC1) or Rheb deletion specifically in the myeloid lineage were generated and subjected to intra-articular injection of collagenase (collagenase-induced osteoarthritis, CIOA) and destabilisation of the medial meniscus (DMM) surgery to induce OA. Cartilage damage and osteophyte size were measured by Osteoarthritis Research Society International score and micro-CT, respectively. mRNA sequencing was performed in M1 and control macrophages. Mice and ATDC5 cells were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in OA.ResultsM1 but not M2-polarised macrophages accumulated in human and mouse OA synovial tissue. TSC1 deletion in the myeloid lineage constitutively activated mechanistic target of rapamycin complex 1 (mTORC1), increased M1 polarisation in synovial macrophages and exacerbated experimental OA in both CIOA and DMM models, while Rheb deletion inhibited mTORC1, enhanced M2 polarisation and alleviated CIOA in mice. The results show that promoting the macrophage M1 polarisation leads to exacerbation of experimental OA partially through secretion of Rspo2 and activation of β-catenin signalling in chondrocytes.ConclusionsSynovial macrophage M1 polarisation exacerbates experimental CIOA partially through Rspo2. M1 macrophages and Rspo2 are potential therapeutic targets for OA treatment.

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Section: Discussionmentioning

confidence: 99%

Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2

et al. 2018

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“…In OA severity and progression, it has been demonstrated that inflammation is mainly mediated by soluble factors and infiltrating immune cells. Macrophages are key effector cells in synovial tissue 11 significantly increasing in number and guiding synovial inflammation 12 . The presence of both M1 and M2 macrophages in human OA synovial tissue has been described in a few studies 21,22 where the focus has mainly been on the levels of their expression rather than on their function.…”

Section: Discussionmentioning

confidence: 99%

“…Macrophages represent the cell population mainly located in the synovial lining layer that significantly increase in number with the increase of synovial inflammation grading from low to high. We have shown that macrophages are key effector cells in the synovial tissue 11 and it has been shown that these cells guide synovial inflammation 12 . Depletion of synovial macrophages in an OA mouse model reduces osteophyte formation and cartilage degeneration, typical features of OA progression 13 .…”

Section: Introductionmentioning

confidence: 99%

Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: in vitro evaluation

Manferdini

Paolella

Gabusi

et al. 2017

Osteoarthritis and Cartilage

128

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“…It has been reported that dexamethasone does not account for increases in chondrogenic activity but may increase osteogenic activity (33). In addition, dexamethasone is a pharmacological agent that has been used to suppress inflammation (34). Certain previous studies added dexamethasone to the medium when preparing cultures; however, it is important to ensure that dexamethasone is not added to cultural environments, as it may suppress chondrocyte proliferation (35,36).…”

Section: Discussionmentioning

confidence: 99%

Effect of naproxen on proliferation and differentiation of primary cell cultures isolated from human cartilage tissue

Karaarslan

Batmaz²,

Yılmaz

et al. 2018

Exp Ther Med

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Non-steroidal anti-inflammatory drugs (NSAIDs) that are applied through oral, injectable or topical routes have been widely used in painful and inflammatory musculoskeletal diseases. The current study aimed to determine whether naproxen, an aryl acetic acid derivative with analgesic and anti-inflammatory effects, has a toxic effect on human chondrocytes. Samples containing monolayer primary chondrocyte cultures were prepared following resection from osteochondral tissues obtained from patients with gonarthrosis. Cell viability, toxicity and proliferation and levels of stage-specific embryonic antigen-1, a precursor to human prechondrocytes, were evaluated spectrophotometrically. The results from the untreated control group were compared with those of the study groups, where naproxen was administered in varying doses (1–1,000 µM). Surface morphologies of the cells were compared using inverted light and environmental scanning electron microscopy. Treatment groups were compared by analysis of variance with Tukey's honest difference post hoc test. P<0.01 was considered to indicate a statistically significant difference. The research revealed significant changes to proliferation and differentiation of chondrocytes in all treatment groups (P<0.01). Naproxen was demonstrated to suppress chondrocyte proliferation and differentiation, which may be an important factor to consider when prescribing this medication to patients.

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Guiding synovial inflammation by macrophage phenotype modulation: an in vitro study towards a therapy for osteoarthritis

Cited by 59 publications

References 49 publications

Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2

Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2

Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: in vitro evaluation

Effect of naproxen on proliferation and differentiation of primary cell cultures isolated from human cartilage tissue

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