Imbalance of M1/M2 macrophages is linked to severity level of knee osteoarthritis

Liu, Baolong; Zhang, Maoquan; Zhao, Jingming; Ma, Zheng; Yang, Hao

doi:10.3892/etm.2018.6852

Cited by 107 publications

(112 citation statements)

References 17 publications

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“…Thus, the expression of both CD86 and CD206 increase with inflammatory stimuli, as a result of increased macrophage recruitment and response to injury (6), and therefore should be carefully analyzed in conjunction with clinical and analytical indicators of disease. Although expression of CD86 and CD206 was reported to associate to M1-and M2-like macrophages in the synovial fluid from normal and OA joints (26), this observation is in disagreement with the profiles of macrophages in the synovium in this and other experimental studies (6,23,25).…”

Section: Intensity Of Expression Did Vary With Degree Of Synovial Infcontrasting

confidence: 77%

“…Specific information regarding macrophage phenotypes in joint disease is limited to in vitro studies, experimental data, or end stage OA. Reports describing comparisons of diseased and healthy joints include extrapolations from other types of arthritides, such as rheumatoid arthritis or are limited to the low numbers of synovial fluid macrophages shedding from the synovium following hyperactivation (6,9,12,23,26,27). Defining patterns of macrophage activation in normal and osteoarthritic synovium is paramount to enhancing the understanding of the roles of macrophages in vivo, and to optimize strategies targeting macrophage-driven joint homeostasis (25).…”

mentioning

confidence: 99%

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Comparative analysis of macrophage activation in the synovium of healthy and osteoarthritic equine joints

Menarim

Gillis

Oliver

et al. 2020

Preprint

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Background: Synovitis is a major component of osteoarthritis and is driven primarily by macrophages. Synovial macrophages are crucial keepers of joint health by driving joint homeostasis, tissue repair and inflammation resolution (M2-like phenotype), but can also induce an inflammatory response (M1-like phenotype) when these regulatory functions are overwhelmed. Macrophage phenotypes in synovium from osteoarthritic and healthy joints are poorly characterized. Defining the patterns of synovial macrophage phenotypes in normal and osteoarthritic joints is paramount for developing targeted therapeutic approaches. The objective of this study was to compare patterns of macrophage activation phenotypes in healthy and osteoarthritic equine joints. We hypothesized that synovium from osteoarthritic joints would have increased M1-like:M2-like ratios compared to normal joints. Methods: Gross evaluation of the articular surfaces, histology (H&E) and immunohistochemistry for M1-like (CD86), M2-like (CD206, IL-10), and pan macrophage (CD14) markers was performed on synovial biopsies from healthy (n=29) and osteoarthritic equine joints (n=26). Cytokines (MCP-1, IL-10, PGE 2 , IL-1β, IL-6, TNF-α, IL-1ra) and growth factors (GM-CSF, SDF-1α+β, IGF-1, and FGF-2) in synovial fluid were quantified. Results: All macrophage markers were co-expressed in all joints with minimal differences between OA and normal joints. Intensity of expression varied with degree of synovial inflammation. CD14, CD86, CD206, and IL-10 were more highly expressed in grossly inflamed osteoarthritic synovium, with CD86 most highly expressed. Synovial fluid MCP-1 was higher in osteoarthritic joints while SDF-1 was lower. Overall, concentrations of synovial fluid IL-10 and PGE2 was not different between OA and normal joints. Increased CD14/CD86/CD206/Il-10 expression in the synovium was associated with synovial hyperplasia, consistent with macrophage recruitment and activation in response to higher demands for repair. Conclusions: Macrophages are not as clearly defined in vivo as they are in vitro . The course of an effective response to injury in joints should start with inflammation and be followed inflammation resolution, both of which centrally driven by macrophages. Combined, our findings suggest that homeostatic mechanisms from synovial macrophages are impaired in OA, resulting in unresolved, chronic joint inflammation. Therapeutic approaches aimed at recovering mechanisms of macrophage-driven synovial homeostasis may be more effective in treating osteoarthritis than simply inhibiting inflammation.

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Section: Intensity Of Expression Did Vary With Degree Of Synovial Infcontrasting

confidence: 77%

mentioning

confidence: 99%

Comparative analysis of macrophage activation in the synovium of healthy and osteoarthritic equine joints

Menarim

Gillis

Oliver

et al. 2020

Preprint

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“…In an animal model of intervertebral disk lesions, immunofluorescence labeling of M1 and M2 macrophages indicated an increase in the proportion of M1 cells as well as an increase in TNF‐α expression, suggesting that M1 polarization plays a critical role in early stages of remodeling . In the case of knee OA, a study analyzing M1 macrophages and M2 macrophages in synovial fluid in normal versus OA knees found a higher ratio of M1/M2 in OA versus normal knees and the ratio was significantly correlated to the Kellgren‐Lawrence grade . Direct confirmation that activated macrophages are present in knee OA was collected by imaging of patients with knee OA with SPECT‐CT and Etarfolatide label, which exclusively binds to activated macrophages .…”

Section: Wound Healing—the Role Of the Macrophagementioning

confidence: 95%

Role of Inflammation and the Immune System in the Progression of Osteoarthritis

Woodell-May

Sommerfeld

2019

Journal Orthopaedic Research

237

161

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Understanding the molecular drivers and feedback loops of osteoarthritis (OA) may provide future therapeutic strategies to modulate the disease progression. The current paradigm of OA is evolving from a purely mechanical disease caused by cartilage wear toward a complex biological response connecting biomechanics, inflammation, and the immune system. The view of OA as a chronic wound highlights the role inflammation plays and also the body's attempts to repair an ongoing injury. Inflammatory signals, including cytokines such as interleukin-1 and tissue necrosis factor α, surface-expressed pattern recognition receptors such as toll-like receptors 2 and 4, complement factors such as C5, as well as pathogen-associated molecular patterns and damage-associated molecular patterns drive the enzymatic cascade that degrades cartilage matrix in OA. Considering the joint as an entire organ, interactions between the cells that reside in the synovium including macrophages and other immune cells, appear to drive enzymatic activity in cartilage, which, in turn, feeds signals back to the synovium that continues stimulating degradation in a feed-forward loop. This review will explore the potential roles of immune cells such as macrophages and T cells in the synovium in both stimulating and modulating the inflammatory response in OA.

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“…Accumulating evidence demonstrates that the imbalance of M1/M2 macrophage polarization plays an essential role in OA. [25] Our previous study demonstrated that M1-and not M2-polarized macrophages accumulate in human and mouse OA synovial tissue. [24] M1 macrophage polarization enhances the release of in ammatory factors, such as IL-6, IL-1β, MMPs, and TNF-α, resulting in promotion of nerve growth factor expression and causing OA pain.…”

Section: Discussionmentioning

confidence: 92%

Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways

Pan

et al. 2020

Preprint

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Synovial macrophage polarization and interactions between chondrocytes and macrophages are essential for osteoarthritis (OA) development. The present study determined the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium. 10-week-old male C57BL/6 mice were randomly assigned to sham-operated, collagenase-induced OA (CIOA)-operated, or CIOA-operated with intraarticular fargesin treatment groups. Fargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by down-regulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Although conditioned medium (CM) from the M1 macrophage treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen X in OA cartilage, it had no direct effect on chondrocyte metabolism in an in vitro study. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling. This study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by down-regulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.

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Imbalance of M1/M2 macrophages is linked to severity level of knee osteoarthritis

Cited by 107 publications

References 17 publications

Comparative analysis of macrophage activation in the synovium of healthy and osteoarthritic equine joints

Comparative analysis of macrophage activation in the synovium of healthy and osteoarthritic equine joints

Role of Inflammation and the Immune System in the Progression of Osteoarthritis

Fargesin ameliorates osteoarthritis via macrophage reprogramming by downregulating MAPK and NF-κB pathways

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