New Druggable Targets for Rheumatoid Arthritis Based on Insights From Synovial Biology

Sandhu, Gurvisha; Thelma, B.K.

doi:10.3389/fimmu.2022.834247

Cited by 14 publications

(8 citation statements)

References 149 publications

(185 reference statements)

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“…Using liquid chromatography coupled with mass spectrometry, T cell epitopes have been identified directly from inflamed synovial tissue, then tested for immunogenicity using patient samples. In one study, it has been noted that a peptide from a protein of P. copri 27 kDa (Pc-p27) stimulated T and B lymphocytes in 40% of patients with rheumatoid arthritis, but not in the control group or in patients with other rheumatic diseases [8,144,145]. This peptide is also presented by an HLA-DR receptor, which is consistent with existing data on HLA-DR and its relationship to the phenomenon of molecular mimicry.…”

Section: Molecular Mimicrysupporting

confidence: 75%

Biomolecular Mechanisms of Autoimmune Diseases and Their Relationship with the Resident Microbiota: Friend or Foe?

et al. 2022

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The use of innovative approaches to elucidate the pathophysiological mechanisms of autoimmune diseases, as well as to further study of the factors which can have either a positive or negative effect on the course of the disease, is essential. In this line, the development of new molecular techniques and the creation of the Human Genome Program have allowed access to many more solutions to the difficulties that exist in the identification and characterization of the microbiome, as well as changes due to various factors. Such innovative technologies can rekindle older hypotheses, such as molecular mimicry, allowing us to move from hypothesis to theory and from correlation to causality, particularly regarding autoimmune diseases and dysbiosis of the microbiota. For example, Prevotella copri appears to have a strong association with rheumatoid arthritis; it is expected that this will be confirmed by several scientists, which, in turn, will make it possible to identify other mechanisms that may contribute to the pathophysiology of the disease. This article seeks to identify new clues regarding similar correlations between autoimmune activity and the human microbiota, particularly in relation to qualitative and quantitative microbial variations therein.

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Section: Molecular Mimicrysupporting

confidence: 75%

Biomolecular Mechanisms of Autoimmune Diseases and Their Relationship with the Resident Microbiota: Friend or Foe?

et al. 2022

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“…Rheumatoid arthritis (RA) is a systemic inflammatory disease whose pathogenesis is often characterized by the infiltration of proinflammatory synovial fibroblasts, elevated frequency of synovial osteoclasts, and progressive joint destruction (Smolen et al, 2016;Zhao et al, 2022). Multiple strategies to inhibit the proliferation of synovial fibroblasts and reinstate synovial homeostasis in RA could provide promising therapeutic directions (Chen et al, 2022b;Ji et al, 2022;Sandhu and Thelma, 2022). Recent studies have reported that the increased risk of RA disease might be associated with the dysfunction of the antioxidant system in fibroblast-like synoviocytes (FLS).…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Current insights into the functional roles of ferroptosis in musculoskeletal diseases and therapeutic implications

Zhang

Yan

Cai

et al. 2023

Front. Cell Dev. Biol.

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Ferroptosis is a novel type of cell death associated with iron accumulation and excessive lipid peroxidation. Elucidating the underlying molecular mechanisms of ferroptosis is intensively related to the development and treatment of multiple diseases, including musculoskeletal disorders. Moreover, in vitro and in vivo studies have shown the importance of oxidative stress in musculoskeletal conditions such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma. Ferroptosis-derived clinical management of musculoskeletal diseases offers tremendous and attractive opportunities. Notably, ferroptosis agonists have been proven to enhance the sensitivity of osteosarcoma cells to conventional therapeutic strategies. In this review, we have mainly focused on the implications of ferroptosis regulation in the pathophysiology and therapeutic response of musculoskeletal disorders. Understanding roles of ferroptosis for controlling musculoskeletal diseases might provide directions for ferroptosis-driven therapies, which could be promising for the development of novel therapeutic strategies.

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“…RA mainly affects synovial joints, with inflammation of the synovial membrane (synovitis) characterized by angiogenesis, hyperplasia of the lining layer, and immune cell infiltration that stimulates local inflammation and, if untreated, can result in joint destruction and disability ( Rivellese and Pitzalis, 2021 ). Progress in therapeutic approaches and understanding of RA pathogenesis have improved patient prognosis and likely remission, while partial/non-response to conventional and biologic therapies in certain patients underlines the need for new therapeutics ( Sandhu and Thelma, 2022 ). Fibroblast-like synoviocytes (FLS) in the synovial lining develop aggressive phenotypes and are a main focus within the RA field, and the proportion of the surface marker CD90 correlates positively with the proportion of synovitis and synovial hypertrophy ( Wu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

RUNX1 Ameliorates Rheumatoid Arthritis Progression through Epigenetic Inhibition of LRRC15

Ding

Mei

et al. 2023

Molecules and Cells

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Leucine-rich repeat containing 15 (LRRC15) has been identified as a contributing factor for cartilage damage in osteoarthritis; however, its involvement in rheumatoid arthritis (RA) and the underlying mechanisms have not been well characterized. The purpose of this study was to explore the function of LRRC15 in RA-associated fibroblastlike synoviocytes (RA-FLS) and in mice with collagen-induced arthritis (CIA) and to dissect the epigenetic mechanisms involved. LRRC15 was overexpressed in the synovial tissues of patients with RA, and LRRC15 overexpression was associated with increased proliferative, migratory, invasive, and angiogenic capacities of RA-FLS and accelerated release of pro-inflammatory cytokines. LRRC15 knockdown significantly inhibited synovial proliferation and reduced bone invasion and destruction in CIA mice. Runt-related transcription factor 1 (RUNX1) transcriptionally represses LRRC15 by binding to core-binding factor subunit beta (CBF-β). Overexpression of RUNX1 significantly inhibited the invasive phenotype of RA-FLS and suppressed the expression of proinflammatory cytokines. Conversely, the effects of RUNX1 were significantly reversed after overexpression of LRRC15 or inhibition of RUNX1-CBF-β interactions. Therefore, we demonstrated that RUNX1-mediated transcriptional repression of LRRC15 inhibited the development of RA, which may have therapeutic effects for RA patients.

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New Druggable Targets for Rheumatoid Arthritis Based on Insights From Synovial Biology

Cited by 14 publications

References 149 publications

Biomolecular Mechanisms of Autoimmune Diseases and Their Relationship with the Resident Microbiota: Friend or Foe?

Biomolecular Mechanisms of Autoimmune Diseases and Their Relationship with the Resident Microbiota: Friend or Foe?

Current insights into the functional roles of ferroptosis in musculoskeletal diseases and therapeutic implications

RUNX1 Ameliorates Rheumatoid Arthritis Progression through Epigenetic Inhibition of LRRC15

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