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

Zhang, Haiyan; Lin, Chuangxin; Zeng, Chun; Wang, Zhenyu; Hua, Wang; Lu, Jiansen; Liu, Xin; Shao, Yan; Zhao, Chang; Pan, Jinhe; Xu, Song; Zhang, Yue; Xie, Denghui; Cai, Daozhang; Bai, Xia

doi:10.1136/annrheumdis-2018-213450

Cited by 275 publications

(254 citation statements)

References 44 publications

(24 reference statements)

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“…OA is a disease which affects all joint tissues, characterized by progressive degeneration of the articular cartilage, neovascular invasion of articular surface, subchondral bone remodeling, osteophyte formation, bone marrow lesions, meniscal damage and synovial inflammation (synovitis) (18,27). Joint effusion is detected in half of patients with OA symptoms and no radiographic findings, indicating that synovitis is not restricted to severe OA only, but is associated with increased pain and dysfunction (28).…”

Section: Articular Cartilage and Inflammationmentioning

confidence: 99%

“…Accumulating evidence suggests that synovial inflammation is correlative with the pathogenesis and progression of OA (27). And articular inflammatory environment is the key factor for initiation and aggregation of cartilage lesion (29).…”

Section: Articular Cartilage and Inflammationmentioning

confidence: 99%

“…Increased vascular density and inflammatory cell infiltration (lymphocytes and macrophages) are common features of OA (31). Macrophage accumulation in the intimal lining, reflecting mostly proliferative synovial tissue, is the principal morphological characteristic of synovitis (27).…”

Section: Articular Cartilage and Inflammationmentioning

confidence: 99%

“…Normal synovium consists of two distinct tissue layers. One is the intimal lining layer with two to three layers of macrophages (type A cells) with phagocytic function and fibroblast-like synoviocytes (type B cells) with secretory function that produces hyaluronan and lubricin (25,26); the other is the synovial sublining layer, composed of fibrous connective tissue and blood vessels, with few lymphocytes or macrophages (27).…”

Section: Articular Cartilage and Inflammationmentioning

confidence: 99%

“…Macrophages, together with fibroblasts, are present in the synovial lining of joints. They are involved in synovial inflammation, and have been shown to play a prominent role in the progression of OA (27). Macrophages are innate immune cells that express MHC class II, which gives them the ability to initiate adaptive immune response through T cell activation.…”

Section: Macrophagesmentioning

confidence: 99%

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Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

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Section: Articular Cartilage and Inflammationmentioning

confidence: 99%

Section: Articular Cartilage and Inflammationmentioning

confidence: 99%

Section: Articular Cartilage and Inflammationmentioning

confidence: 99%

Section: Articular Cartilage and Inflammationmentioning

confidence: 99%

Section: Macrophagesmentioning

confidence: 99%

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Macrophage: A Potential Target on Cartilage Regeneration

et al. 2020

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Regulation of Synovial Macrophages Polarization by Mimicking Efferocytosis for Therapy of Osteoarthritis

Yang

et al. 2022

Adv Funct Materials

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The progression of osteoarthritis is associated with chronic synovitis caused by synovial macrophage infiltration and proinflammatory M1 polarization. Accordingly, repolarization of macrophages from the M1 to M2 phenotype by nanoagents is proposed as a potential treatment strategy. However, achieving adequate effects using intra-articular injected agents is challenging due to the rapid drug clearance from the joint space and poor efficiency of nanoparticles endocytosis by synovial macrophage cells. Herein, apoptotic chondrocyte membrane-coated, quercetin-loaded metalorganic framework nanoparticles as immunomodulators for treating osteoarthritis are reported. The apoptotic chondrocyte membrane-camouflaged nanoparticles containing various natural "eat me" signals can be easily disguised as chondrocyte apoptotic bodies in the joints, and thus are more easily phagocytized by synovial macrophages similarly to efferocytosis. Furthermore, the released quercetin promotes the polarization of synovial macro phages to the M2 phenotype and also inhibites the apoptosis of articular chondrocytes. In vivo results suggest that such a "Trojan horse" strategy can extend the retention time of nanoparticles in osteoarthritis joints and improve treatment efficacy. Collectively, it is hoped that this study can offer a potential and universal platform for engineered cell membranecoated nanoparticles to resolve inflammation by simulating specific inflammatory processes.

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A Bionic Thermosensitive Sustainable Delivery System for Reversing the Progression of Osteoarthritis by Remodeling the Joint Homeostasis

Tong,

Song,

Liu

et al. 2024

Adv Healthcare Materials

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Although the pathogenesis of osteoarthritis (OA) is unclear, inflammatory cytokines are related to its occurrence. However, few studies focused on the therapeutic strategies of regulating joint homeostasis by simultaneously remodeling anti‐inflammatory and immunomodulatory microenvironment. Fibroblast growth factor 18 (FGF18) is the only disease‐modifying OA drug (DMOAD) with a potent ability and high efficiency in maintaining the phenotype of chondrocytes within cell culture models. However, its potential role in the immune microenvironment remains unknown. Besides, information on an optimal carrier, whose interface and chondral‐biomimetic microenvironment mimic the native articular tissue, is still lacking, which substantially limits the clinical efficacy of FGF18. Herein, to simulate the cartilage matrix, chondroitin sulfate (ChS)‐based nanoparticles (NPs) were integrated into poly(D, L‐lactide)‐poly(ethylene glycol)‐poly(D, L‐lactide) (PLEL) hydrogels to develop a bionic thermosensitive sustainable delivery system. Electrostatically self‐assembled ChS and ε‐poly‐l‐lysine (EPL) NPs were prepared for the bioencapsulation of FGF18. This bionic delivery system suppressed the inflammatory response in IL‐1β‐mediated chondrocytes, promoted macrophage M2 polarization, and inhibited M1 polarization, thereby ameliorating cartilage degeneration and synovitis in OA. Thus, the ChS‐based hydrogel system offers a potential strategy to regulate the chondrocyte‐macrophage crosstalk, thus re‐establishing the anti‐inflammatory and immunomodulatory microenvironment for OA therapy.This article is protected by copyright. All rights reserved

show abstract

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

Cited by 275 publications

References 44 publications

Macrophage: A Potential Target on Cartilage Regeneration

Macrophage: A Potential Target on Cartilage Regeneration

Regulation of Synovial Macrophages Polarization by Mimicking Efferocytosis for Therapy of Osteoarthritis

A Bionic Thermosensitive Sustainable Delivery System for Reversing the Progression of Osteoarthritis by Remodeling the Joint Homeostasis

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