Interleukin‐21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen‐induced arthritis

Kwok, Seung‐Ki; Cho, Mi‐La; Park, Mi-Kyung; Oh, Hyeyoung; Park, Jin‐Sil; Her, Yang-Mi; Lee, Seon‐Yeong; Youn, Jeehee; Park, Kyung Su; Kim, Sung-Il; Kim, Ho-Youn; Park, Sung-Hwan

doi:10.1002/art.33390

Cited by 106 publications

(88 citation statements)

References 39 publications

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“…Taken together, the results from both in vitro and in vivo experiments suggested evaluating effects of Il-21 in human CNS autoimmune demyelinating disease. It has been reported that serum Il-21 levels were elevated in many autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis and Sjogren's syndrome 30,31 . Consistent with previous findings, we demonstrated a high level of serum Il-21 in NMO THe CANADIAN JOURNAl OF NeUROlOGICAl SCIeNCeS 818…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Zhong²,

Wang³

et al. 2012

Can. J. Neurol. Sci.

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Neuromyelitis optica (NMO) and Multiple sclerosis (MS) are two typical inflammatory demyelinating diseases of the central nervous system (CNS) with complex pathogenesis, and they share many similarities. Neuromyelitis optica was considered an optic-spinal form of MS until specific antibodies (NMO-IgG) were suggested to be a biomarker of NMO, distinguishing it from conventional MS 1 . T cells have emerged as a key player in the pathogenesis of MS 2 . We also found increased levels of CD4 + T cells in NMO patients 3 . Simultaneously, B cells are believed to play an important role in the pathogenesis of these diseases. A role of B cells in MS pathogenesis has been suggested by the presence of oligoclonal immunoglobulin bands (OCBs) in cerebrospinal fluid (CSF) 4,5 . In addition, NMO-IgG is compelling evidence for B cells involvement in NMO pathogenesis 6 . Moreover, therapies which eliminate antibodies ABSTRACT: Background: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are inflammatory demyelinating diseases of human central nervous system (CNS) with complex pathogenesis. Il-21/Il-21R regulates activation, proliferation and survival of both T cells and B cells, which are involved in the pathogenesis of NMO and MS. High levels of serum Il-21 were observed in NMO patients. However, concentration of cerebrospinal fluid (CSF) Il-21 in MS and NMO patients still remain unknown. Object: To detect the CSF concentration of Il-21 in NMO and MS patients and to evaluate its relationship with disease activity, particularly concerned about its impact on humoral immunity. Methods: CSF Il-21 was detected by an enzyme-linked immunosorbent assay (elISA) in NMO patients (n=21), MS patients (n=20) and controls (n=16). Results: CSF concentration of the Il-21 was noticeably elevated in NMO (p=0.012) and borderline significantly increased in MS (p=0.115). In addition, this occurrence was associated with humoral immune activity as shown by a correlation between Il-21 and complement in NMO cohort (p=0.023) and high Il-21 levels in autoantibodypositive subgroup (p=0.027). Conclusions: The concentration of CSF Il-21 was noticeably elevated and might have a positive correlation with humoral immune activity in NMO. RÉSUMÉ: Les niveaux d'IL-21 du liquide céphalo-rachidien dans

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Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Zhong²,

Wang³

et al. 2012

Can. J. Neurol. Sci.

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“…IL-21, a new member of the type 1 cytokine superfamily, promotes osteoclastogenesis in RA (Ref. 215) and has been suggested as target for immune-mediated diseases, especially for preventing bone destruction (Ref. As discussed throughout this review, research into the molecular pathogenesis of periodontitis is continuously producing novel and significant results.…”

Section: Research In Progress and Conclusionmentioning

confidence: 99%

Inflammatory mediators in the pathogenesis of periodontitis

Yucel‐Lindberg

Båge

2013

Expert Rev. Mol. Med.

360

334

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Periodontitis is a chronic inflammatory condition of the periodontium involving interactions between bacterial products, numerous cell populations and inflammatory mediators. It is generally accepted that periodontitis is initiated by complex and diverse microbial biofilms which form on the teeth, i.e. dental plaque. Substances released from this biofilm such as lipopolysaccharides, antigens and other virulence factors, gain access to the gingival tissue and initiate an inflammatory and immune response, leading to the activation of host defence cells. As a result of cellular activation, inflammatory mediators, including cytokines, chemokines, arachidonic acid metabolites and proteolytic enzymes collectively contribute to tissue destruction and bone resorption. This review summarises recent studies on the pathogenesis of periodontitis, with the main focus on inflammatory mediators and their role in periodontal disease.

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“…IL-7 induces overexpression of RANKL in T lymphocytes and its blockade significantly reduces monocyte attraction, osteoclast differentiation and bone erosion in CIA [71]. IL-21 stimulates osteoclastogenesis through an induction of RANKL in CD4 + T lymphocytes, and is upregulated in the synovia and sera of RA patients [72]. Although its role in osteoclastogenesis is still controversial, IL-18 is known to induce M-CSF, GM-CSF, RANKL and OPG in synovial fibroblasts and/or T lymphocytes [73].…”

Section: Effect Of Arthritic Mediators On Osteoclast Progenitorsmentioning

confidence: 99%

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis

Šućur

Katavić

Kelava

et al. 2014

International Orthopaedics (SICOT)

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The inflammatory milieu favors recruitment and activation of osteoclasts, and leads to bone destruction as a serious complication associated with arthritis and with other inflammatory processes.The frequency and activity of osteoclast progenitors (OCPs) correspond to arthritis severity, and may be used to monitor disease progression and bone resorption, indicating the need for detailed characterization of the discrete OCP subpopulations. Collectively, current studies suggest that the most potent murine bone marrow OCP population can be identified among lymphoid negative population within the immature myeloid lineage cells, as B220 -CD3 -CD11b -/lo CD115 + CD117 + CX3CR1 + and possibly also Ter119 -CD11c -CD135 lo Ly6C + RANK -. In the peripheral blood OCP population bears the monocytoid phenotype B220 -CD3 -NK1.1 -CD11b + Ly-6C hi CD115 + CX3CR1 + , presumably expressing RANK in committed OCPs. Much less is known about human OCPs and their regulation in arthritis, but the circulating OCP subset is, most probably, comprised among the lymphoid negative population (CD3 -CD19 -CD56 -), within immature monocyte subset (CD11b + CD14 + CD16 -), expressing receptors for M-CSF and RANKL (CD115 + RANK + ). Our preliminary data confirmed positive association between the proportion of peripheral blood OCPs, defined as CD3 -CD19 -CD56 -CD11b + CD14 + , and the disease activity score (DAS28) in the follow-up samples from patient with psoriatic arthritis receiving anti-TNF therapy. In addition, we reviewed cytokines and chemokines which, directly or indirectly, activate OCPs and enhance their differentiation potential, thus mediating osteoresorption.Control of the activity and migratory behavior of OCPs as well as the identification of crucial bone/joint chemotactic mediators represent promising therapeutic targets in arthritis.Keyword: osteoclast progenitors, arthritis, inflammation, cytokines, chemokines, osteoresorption 3 Inflammation induced bone lossBone is a highly dynamic tissue important for its mechanical and metabolic functions, and characterized by rapid response to numerous physical, endocrine and paracrine stimuli in physiological and pathological conditions. Among others signals, osteoresorptive mediators (such as interleukin (IL)-1, IL-6, IL-15, IL-17, IL, 21, IL-33, tumor necrosis factor (TNF)-α and receptor activator of nuclear factor-κB ligand (RANKL), CCL2, CXCL12) produced by inflammatory/immune cells create conditions that promote maturation and function of osteoclasts [1][2][3][4]. Bone resorption and osteolysis are the prominent features and causes of substantial morbidity in inflammatory processes associated with arthritis as well as with localized bacterial infections of bone and adjacent tissues, peri-prosthetic loosening, vasculitis, connective tissue diseases, chronic viral infections and inflammatory bowel diseases [5][6][7][8]. Bone resorption in arthritisInflammatory arthritides comprise a heterogeneous group of joint disorders that are characterized by chronic inflammatory response as we...

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Interleukin‐21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen‐induced arthritis

Cited by 106 publications

References 39 publications

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Cerebrospinal Fluid IL-21 Levels in Neuromyelitis Optica and Multiple Sclerosis

Inflammatory mediators in the pathogenesis of periodontitis

Induction of osteoclast progenitors in inflammatory conditions: key to bone destruction in arthritis

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