scholarly journals The Roles of TNFRSF11B Genes as a Trigger for Secondary Osteoporosis in Rheumatoid Arthritis Cases

2021 ◽  
Vol 10 (3) ◽  
pp. 234-248
Author(s):  
Nur A. Ali ◽  
Dika P. Destiani ◽  
Riezki Amalia
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Remodeling ◽  
Gene Polymorphisms ◽  
Osteoclast Differentiation ◽  
Autoimmune Disorder ◽  
Nuclear Factor Κb ◽  
Secondary Osteoporosis ◽  
Cochrane Library ◽  
Synovial Joint ◽  
Persistent Inflammation

Rheumatoid arthritis (RA) is an autoimmune disorder responsible for widespread and persistent inflammation of the synovial joint lining. Hence, victims are prone to greater risk of developing secondary osteoporosis (OP), a common complication of arthritis. The global prevalence of secondary OP among RA patients is estimated between 22-36%, although certain genetic polymorphisms pose a possible influence. Also, bone remodeling is closely related to the receptor activator nuclear factor-κB ligand (RANKL)/RANK and osteoprotegerin (OPG). The variables play a significant role in osteoclastogenesis, due to the ability of OPG to inhibit osteoclast differentiation and activation. This literature review discusses the relationship of TNFRSF11B gene polymorphisms that encode OPG protein with the risk of developing secondary osteoporosis in RA patients. The research method encompassed exploring similar articles from Pubmed, Cochrane Library, and Medline, using particular keywords, such as “TNFRSF11B polymorphism”, “osteoprotegerin polymorphism”, “rheumatoid arthritis” and “secondary osteoporosis”. Several distinct conclusions were obtained after analyzing the effects of TNFRSF11B gene polymorphisms on secondary OP in RA cases. Furthermore, the TNFRSF11B gene showed various polymorphisms closely related to bone remodeling, including C950T, G1181C, A163G, T245G and rs4876869.

Emerging Role of Extracellular Vesicles in Bone Remodeling

2018 ◽  
Vol 97 (8) ◽  
pp. 859-868 ◽  
Author(s):  
M. Liu ◽  
Y. Sun ◽  
Q. Zhang
Keyword(s):  
Bone Remodeling ◽  
Extracellular Vesicles ◽  
Transforming Growth Factor ◽  
Tooth Development ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Transforming Growth Factor Β1 ◽  
Bone Diseases ◽  
Bioactive Molecules

Extracellular vesicles (EVs), as nanometer-scale particles, include exosomes, microvesicles, and apoptotic bodies. EVs are released by most cell types, such as bone marrow stem cells, osteoblasts, osteoclasts, and immune cells. In bone-remodeling microenvironments, EVs deliver specific proteins (e.g., tenascin C and Sema4D), microRNAs (e.g., miR-214-3p, miR-183-5p, and miR-196a), and other growth factors (e.g., bone morphogenetic protein 1 to 7 and transforming growth factor β1) to osteoblasts and regulate bone formation. In addition, EVs can deliver cytokines, such as RANK (receptor activator of nuclear factor κB) and RANKL (RANK ligand), and microRNAs, such as miR-218 and miR-148a, to modulate osteoclast differentiation during bone resorption. EVs also transfer bioactive molecules and have targeted therapies in bone-related diseases. Moreover, bioactive molecules in EVs are biomarkers in bone-related diseases. We highlight the emerging role of EVs in bone remodeling during physiologic and pathologic conditions and summarize the role of EVs in tooth development and regeneration. At the end of this review, we discuss the challenges of EV application in the treatment of bone diseases.

scholarly journals Interleukin (IL)-25 suppresses IL-22 induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway

2020 ◽  
Author(s):  
Hong Ki Min ◽  
Ji-Yeon Won ◽  
Bo-Mi Kim ◽  
Kyung-Ann Lee ◽  
Seoung-Joon Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
P38 Mapk ◽  
Human Peripheral Blood ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Blood Monocytes ◽  
Rankl Expression

Abstract Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, as well as synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL + M-CSF, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis. Results Serum and synovial IL-25 levels in RA were up-regulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers. Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.

scholarly journals The association between RANK, RANKL and OPG gene polymorphisms and the risk of rheumatoid arthritis: a case-controlled study and meta-analysis

2019 ◽  
Vol 39 (6) ◽  
Author(s):  
Haoyu Yang ◽  
Weixi Liu ◽  
Xindie Zhou ◽  
Huan Rui ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
Nuclear Factor Κb ◽  
Controlled Study ◽  
Female Age ◽  
Flight Mass Spectrometry ◽  
Base Extension ◽  
Different Populations ◽  
Rank Gene

Abstract The receptor activator of nuclear factor-κB (RANK) and the osteoprotegerin (OPG) cascade system have been reported to be essential in osteoclastogenesis. In recent years, several studies have investigated the association between polymorphisms of RANK, its ligand RANKL and OPG genes and the risk of rheumatoid arthritis (RA) in different populations. However, the results arising from these studies were conflicting. To determine the association between RANK, RANKL and OPG gene polymorphisms and the risk of RA. We conducted a hospital-based case-controlled study in Changzhou with 574 RA cases and 804 controls. The genotyping of RANK gene rs1805034 polymorphism was conducted by single base extension combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). We also undertook a meta-analysis of the literature referring to polymorphisms of RANK, RANKL and OPG genes and RA risk. This case-controlled study found that the polymorphism in the RANK gene rs1805034 was not related to RA risk. Stratification analyses by sex and age suggested that RANK gene rs1805034 polymorphism was not associated with the risk of RA among groups of male, female, age ≤ 55 and age > 55. Our meta-analysis found that the rs2277438 polymorphism in RANKL gene increased the risk of RA, whereas RANK gene rs1805034, OPG gene rs3102735, OPG gene rs2073618, OPG gene rs3134069 polymorphisms were not related to RA susceptibility. In conclusion, this case-controlled study and meta-analysis indicated that the RANKL gene rs2277438 polymorphism increased the RA risk, and that RANK gene rs1805034, OPG gene rs3102735, OPG gene rs2073618, OPG gene rs3134069 polymorphisms were not related to RA risk.

scholarly journals Interleukin (IL)-25 suppresses IL-22 induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway

2019 ◽  
Author(s):  
Hong Ki Min ◽  
Ji-Yeon Won ◽  
Bo-Mi Kim ◽  
Kyung-Ann Lee ◽  
Seoung-Joon Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
P38 Mapk ◽  
Human Peripheral Blood ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Blood Monocytes ◽  
Rankl Expression

Abstract Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA).Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, as well as synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis.Results Serum and synovial IL-25 levels in RA were up-regulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers.Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.

scholarly journals Jintiange Capsules Ameliorate Osteoarthritis by Modulating Subchondral Bone Remodeling and Protecting Cartilage Against Degradation

2021 ◽  
Vol 12 ◽  
Author(s):  
Chenyang Zhuang ◽  
Zixiang Wang ◽  
Weisin Chen ◽  
Hanquan Wang ◽  
Bo Tian ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Subchondral Bone ◽  
Cruciate Ligament ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Joint Disease ◽  
Chondrocyte Apoptosis ◽  
And Cartilage

Osteoarthritis (OA) is the most prevalent joint disease worldwide, making it a major cause of pain and disability. Identified as a chronic and progressive disease, effective treatment at the early stages of OA has become critical to its management. Jintiange (Jtg) capsules are a traditional Chinese medicine produced from multiple organic components of various animal bones and routinely used to treat osteoporosis in China. However, the effect of Jtg on subchondral bone and cartilage degeneration in OA remains unknown. The purpose of the present study was to investigate the biomolecular role and underlying mechanisms of Jtg in OA progression. Herein, we found that Jtg inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and it functions through the NF-κB signaling pathway. Jtg also inhibited chondrocyte apoptosis via reducing the reactive oxygen species concentration in these cells. Moreover, in vivo evaluation revealed that Jtg significantly attenuates subchondral bone remodeling and cartilage destruction in anterior cruciate ligament transection (ACLT) mouse models. Taken together, our data demonstrate that Jtg inhibits osteoclast differentiation in subchondral bone and chondrocyte apoptosis in cartilage, supporting its potential therapeutic value for treating OA.

scholarly journals Interleukin (IL)-25 suppresses IL-22-induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Hong Ki Min ◽  
Ji-Yeon Won ◽  
Bo-Mi Kim ◽  
Kyung-Ann Lee ◽  
Seoung-Joon Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
P38 Mapk ◽  
Human Peripheral Blood ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Blood Monocytes ◽  
Rankl Expression

Abstract Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA). Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, and synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL + M-CSF, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis. Results Serum and synovial IL-25 levels in RA were upregulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers. Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.

scholarly journals Examining the relationship between rheumatoid arthritis, multimorbidity and adverse health-related outcomes: A systematic review protocol

2020 ◽  
Vol 10 ◽  
pp. 2235042X2090665
Author(s):  
Jordan Canning ◽  
Stefan Siebert ◽  
Bhautesh D Jani ◽  
Frances S Mair ◽  
Barbara I Nicholl
Keyword(s):  
Rheumatoid Arthritis ◽  
Systematic Review ◽  
Autoimmune Disorder ◽  
Cochrane Library ◽  
Systemic Complications ◽  
Registration Number ◽  
Health Related ◽  
Review Protocol ◽  
Meta Analyses ◽  
The Cochrane Library

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by articular inflammation and systemic complications. Multimorbidity (the presence of two or more long-term health conditions) is highly prevalent in people with RA but the effect of multimorbidity on mortality and other health-related outcomes is poorly understood. Objective: To determine what is known about the effect, if any, of multimorbidity on mortality and health-related outcomes in individuals with RA. Design: Systematic review of the literature. The following electronic medical databases will be searched: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, The Cochrane Library and Scopus. Included studies will be quality appraised using the Quality in Prognostic Studies tool developed by the Cochrane Prognosis Methods Group. A narrative synthesis of findings will be undertaken and meta-analyses considered, if appropriate. This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols 2015 guidelines, ensuring the quality of the review. Conclusions: Understanding the influence of multimorbidity on mortality and other health-related outcomes in RA will provide an important basis of knowledge with the potential to improve future clinical management of RA. PROSPERO registration number: CRD42019137756.

scholarly journals B cell autoimmunity and bone damage in rheumatoid arthritis

Reumatismo ◽  
2016 ◽  
Vol 68 (3) ◽  
pp. 117 ◽  
Author(s):  
S. Bugatti ◽  
L. Bogliolo ◽  
C. Montecucco ◽  
A. Manzo
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
Bone Remodeling ◽  
Mechanistic Explanation ◽  
Multiple Roles ◽  
Persistent Inflammation ◽  
Bone Damage ◽  
Substantial Progress ◽  
Citrullinated Protein ◽  
Made In

Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease associated with significant bone damage. Pathological bone remodeling in RA is primarily driven by persistent inflammation. Indeed, pro-inflammatory cytokines stimulate the differentiation of bone-resorbing osteoclasts and, in parallel, suppress osteoblast function, resulting in net loss of bone. Abating disease activity thus remains the major goal of any treatment strategy in patients with RA. Autoantibody-positive patients, however, often show a rapidly progressive destructive course of the disease, disproportionate to the level of inflammation. The epidemiological association between RA-specific autoantibodies, in particular anti-citrullinated protein autoantibodies, and poor structural outcomes has recently found mechanistic explanation in the multiple roles that B cells play in bone remodeling. In this review, we will summarize the substantial progress that has been made in deciphering how B cells and autoantibodies negatively impact on bone in the course of RA, through both inflammation-dependent and independent mechanisms.

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