scholarly journals Fc Gamma Receptors as Regulators of Bone Destruction in Inflammatory Arthritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuyue Zuo ◽  
Guo-Min Deng
Keyword(s):  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Therapeutic Targets ◽  
Bone Destruction ◽  
Signaling Molecules ◽  
Fc Gamma Receptors ◽  
Dual Roles ◽  
Signaling Transduction

Bone erosion is one of the primary features of inflammatory arthritis and is caused by excessive differentiation and activation of osteoclasts. Fc gamma receptors (FcγRs) have been implicated in osteoclastogenesis. Our recent studies demonstrate that joint-deposited lupus IgG inhibited RANKL-induced osteoclastogenesis. FcγRI is required for RANKL-induced osteoclastogenesis and lupus IgG-induced signaling transduction. We reviewed the results of studies that analyzed the association between FcγRs and bone erosion in inflammatory arthritis. The analysis revealed the dual roles of FcγRs in bone destruction in inflammatory arthritis. Thus, IgG/FcγR signaling molecules may serve as potential therapeutic targets against bone erosion.

scholarly journals NRF2 Is an Upstream Regulator of MYC-Mediated Osteoclastogenesis and Pathological Bone Erosion

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2133
Author(s):  
Peter Sang Uk Park ◽  
Se Hwan Mun ◽  
Steven L. Zeng ◽  
Haemin Kim ◽  
Seyeon Bae ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Bone Destruction ◽  
Fine Tuning ◽  
Related Factor ◽  
Nuclear Factor ◽  
Upstream Regulator

Osteoclasts are the sole bone-resorbing cells that play an essential role in homeostatic bone remodeling and pathogenic bone destruction such as inflammatory arthritis. Pharmacologically targeting osteoclasts has been a promising approach to alleviating bone disease, but there remains room for improvement in mitigating drug side effects and enhancing cell specificity. Recently, we demonstrated the crucial role of MYC and its downstream effectors in driving osteoclast differentiation. Despite these advances, upstream regulators of MYC have not been well defined. In this study, we identify nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor known to regulate the expression of phase II antioxidant enzymes, as a novel upstream regulator of MYC. NRF2 negatively regulates receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis through the ERK and p38 signaling-mediated suppression of MYC transcription. Furthermore, the ablation of MYC in osteoclasts reverses the enhanced osteoclast differentiation and activity in NRF2 deficiency in vivo and in vitro in addition to protecting NRF2-deficient mice from pathological bone loss in a murine model of inflammatory arthritis. Our findings indicate that this novel NRF2-MYC axis could be instrumental for the fine-tuning of osteoclast formation and provides additional ways in which osteoclasts could be therapeutically targeted to prevent pathological bone erosion.

scholarly journals Critical Roles for Interleukin 1 and Tumor Necrosis Factor α in Antibody-induced Arthritis

2002 ◽  
Vol 196 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Hong Ji ◽  
Allison Pettit ◽  
Koichiro Ohmura ◽  
Adriana Ortiz-Lopez ◽  
Veronique Duchatelle ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Inflammatory Cytokines ◽  
Inflammatory Arthritis ◽  
Tumor Necrosis ◽  
Environmental Changes ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Tnf Α ◽  
Necrosis Factor

In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)–α was also required, although seemingly less critically than IL-1, because a proportion of TNF-α–deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFα for bone destruction. The variability in the requirement for TNF-α, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes.

scholarly journals Lupus IgG Induces Synovial Inflammation but Inhibits Bone Erosions in SLE Arthritis

2020 ◽  
Vol 3 (4) ◽  
Keyword(s):  
Therapeutic Target ◽  
Inflammatory Arthritis ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Synovial Inflammation ◽  
Bone Erosions ◽  
Published Paper ◽  
Novel Therapeutic

Bone erosion is an important feature of inflammatory arthritis. It remains unknown why lupus arthritis lacks bone erosion and destruction. Our recent published paper presents the interesting discovery that joint deposited lupus IgG triggers synovitis but suppresses osteoclastogenesis which is responsible for bone destruction. In this paper, data show that joint deposited lupus IgG induces synovitis through FcgRI on monocytes/macrophages and blocks RANKL-induced osteoclastogenesis through competing for FcgRI binding with RANKL. This study promotes understanding the pathogenesis of lupus arthritis and provides a novel therapeutic target of FcgRI to inhibit bone destruction in inflammatory arthritis.

Innate Lymphoid Cells Type 2 Attenuate Inflammatory Arthritis and Protect from Bone Destruction

2018 ◽  
Author(s):  
Yasunori Omata ◽  
SSbastien Lucas ◽  
Kerstin Sarter ◽  
Darja Andreev ◽  
Tatjana Primbs ◽  
...  
Keyword(s):  
Inflammatory Arthritis ◽  
Bone Destruction ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells

Osteosarcoma of the jaws: a literature review

2020 ◽  
Vol 16 ◽  
Author(s):  
Francesco Ricotta ◽  
Massimo Bassi ◽  
Nicola Tomasetti ◽  
Angelo Campobassi ◽  
Vincenzo Maiolo ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
State Of The Art ◽  
Bone Erosion ◽  
Tumor Resection ◽  
Bone Destruction ◽  
Cell Type ◽  
Complete Tumor Resection ◽  
Predominant Cell Type ◽  
Bone Changes ◽  
Complete Tumor

: Osteosarcoma of the jaws (OSJ) is a relatively rare disease, accounting for between 2% and 10% of all cases of osteosarcoma, it is morphologically and radiologically identical to the trunk and extremity variant, but distinct in several crucial aspects. : The lesion is characterized by sarcomatous cells which produces a variable amount of osteoid bone. It arises centrally within the bone and can be subdivided into osteoblastic, chondroblastic and fibroblastic subtype, depending on the predominant cell type. : Radiographically, these tumors display a spectrum of bone changes from well-demarcated borders to lytic bone destruction with indefinite margins and variable cortical bone erosion or, in some cases, images of sclerotic bone. Therapeutic options for OSJ include surgery, chemotherapy and radiotherapy, which are employed according to age of the patient, histological classification and localization of the tumor. Today there is no a general consensus in the treatment guidelines for the OSJ though surgery represents the key of the treatment. The main prognostic factor deeply influencing the patient's prognosis remains the complete tumor resection with negative surgical margins. : The aim of the present review is to describe the state of the art regarding diagnostic and surgical treatment aspects of the primary osteosarcoma of the jaws.

scholarly journals Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems

2017 ◽  
Vol 97 (4) ◽  
pp. 1295-1349 ◽  
Author(s):  
Kazuo Okamoto ◽  
Tomoki Nakashima ◽  
Masahiro Shinohara ◽  
Takako Negishi-Koga ◽  
Noriko Komatsu ◽  
...  
Keyword(s):  
Bone Cells ◽  
Bone Erosion ◽  
Bone Destruction ◽  
T Cell Subsets ◽  
Cellular Interactions ◽  
Hematopoietic Stem ◽  
Interdisciplinary Field ◽  
Receptor Activator ◽  
Two Systems ◽  
Regulatory Functions

The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems. Here we review the function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions. Osteoimmunology has become indispensable for understanding the pathogenesis of a number of diseases such as rheumatoid arthritis (RA). We review the various osteoimmune pathologies, including the bone destruction in RA, in which pathogenic helper T cell subsets [such as IL-17-expressing helper T (Th17) cells] induce bone erosion through aberrant RANKL expression. We also focus on cellular interactions and the identification of the communication factors in the bone marrow, discussing the contribution of bone cells to the maintenance and regulation of hematopoietic stem and progenitors cells. Thus the time has come for a basic reappraisal of the framework for understanding both the immune and bone systems. The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system.

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