Nintedanib ameliorates osteoarthritis in mice by inhibiting synovial inflammation and fibrosis caused by <scp>M1</scp> polarization of synovial macrophages via the <scp>MAPK</scp>/<scp>PI3K‐AKT</scp> pathway

Yan, Jiangbo; Feng, Gangning; Yang, Yong; Zhao, Xin; Ma, Long; Guo, Haohui; Chen, Xiaolei; Wang, Hui; Chen, Zhirong; Jin, Qunhua

doi:10.1096/fj.202300944rr

Cited by 8 publications

(2 citation statements)

References 44 publications

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“…The mechanism involves inhibition of the PI3K-AKT signalling axis [ 15 ]. One study demonstrated that the inhibition of M1 polarization in osteoarthritis synovial macrophages by nintedanib is mediated by the MAPK/PI3K-AKT pathway, resulting in reduced articular cartilage degeneration [ 176 ]. The inhibitory effect of CeO NPs on ROS-induced MAPK production in macrophages may also contribute to the M2 polarization of macrophages.…”

Section: Effects Of Re Nms On Osteogenesis and The Underlying Mechanismsmentioning

confidence: 99%

Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms

Chen,

Zhou,

et al. 2024

J Nanobiotechnol

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Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research. Graphical abstract

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Section: Effects Of Re Nms On Osteogenesis and The Underlying Mechanismsmentioning

confidence: 99%

Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms

Chen,

Zhou,

et al. 2024

J Nanobiotechnol

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“…Another important pathway involved in M1 macrophage polarization is MAPKs signalling, which includes the ERK1/2, JNK, and p38 kinases. Downregulation of the phosphorylation levels of ERK, JNK, and p38 by nintedanib inhibited M1 macrophage polarization in the inflamed synovium ( Yan et al, 2023 ).…”

Section: Functions Of Macrophage Polarization In Rheumatoid Arthritismentioning

confidence: 99%

Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis

Deng,

Xu,

Wang

et al. 2024

Front. Pharmacol.

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Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation, cartilage destruction, pannus formation and bone erosion. Various immune cells, including macrophages, are involved in RA pathogenesis. The heterogeneity and plasticity of macrophages render them pivotal regulators of both the induction and resolution of the inflammatory response. Predominantly, two different phenotypes of macrophages have been identified: classically activated M1 macrophages exacerbate inflammation via the production of cytokines, chemokines and other inflammatory mediators, while alternatively activated M2 macrophages inhibit inflammation and facilitate tissue repair. An imbalance in the M1/M2 macrophage ratio is critical during the initiation and progression of RA. Macrophage polarization is modulated by various transcription factors, epigenetic elements and metabolic reprogramming. Curcumin, an active component of turmeric, exhibits potent immunomodulatory effects and is administered in the treatment of multiple autoimmune diseases, including RA. The regulation of macrophage polarization and subsequent cytokine production as well as macrophage migration is involved in the mechanisms underlying the therapeutic effect of curcumin on RA. In this review, we summarize the underlying mechanisms by which curcumin modulates macrophage function and polarization in the context of RA to provide evidence for the clinical application of curcumin in RA treatment.

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Development of a novel rabbit model for femoroacetabular impingement through surgically induced acetabular overcoverage

Zhang,

Gao,

Zhou

et al. 2024

Journal Orthopaedic Research

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There is a lack of validated small animal models for femoroacetabular impingement (FAI) that induce intra‐articular lesions and cause osteoarthritis (OA) progression. The gene expression profile of articular cartilage in patients with FAI has not been characterized in animal studies. The purpose of this study is to describe a novel rabbit model for FAI with validated induction of intra‐articular lesions and OA progression and to characterize the gene expression pattern in impinged cartilage using this model. Thirty 6‐month‐old New Zealand White rabbits underwent unilateral endobutton implant placement at the acetabular rim to surgically create overcoverage. Radiological assessment confirmed secure placement of endobutton at the acetabular rim for all operated hips with a mean alteration in lateral center‐edge angle (ΔLCEA) of 16.2 ± 6.6°. Gross inspection revealed secondary cartilage injuries in the anterosuperior region of the femoral head for the operated hips. Cartilage injuries were shown to exacerbate with increased impingement duration, as demonstrated by the modified Outerbridge scores and Mankin scores. Immunostaining and quantitative real‐time polymerase chain reaction revealed elevated expression of inflammatory, anabolic and catabolic genes in impinged cartilage. RNA sequencing analysis of cartilage tissue revealed a distinct transcriptome profile and identified C‐KIT, CD86, and CD68 as central markers. Our study confirmed that the novel rabbit FAI model created acetabular overcoverage and produced articular cartilage injury at the impingement zone. Cartilage from the impingement zone demonstrated a heightened metabolic state, corroborating with the gene expression pattern observed in patients with FAI.

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Nintedanib ameliorates osteoarthritis in mice by inhibiting synovial inflammation and fibrosis caused by M1 polarization of synovial macrophages via the MAPK/PI3K‐AKT pathway

Cited by 8 publications

References 44 publications

Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms

Systematic review of the osteogenic effect of rare earth nanomaterials and the underlying mechanisms

Immunomodulatory effects of curcumin on macrophage polarization in rheumatoid arthritis

Development of a novel rabbit model for femoroacetabular impingement through surgically induced acetabular overcoverage

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