Different Modulatory Effects of IL-17, IL-22, and IL-23 on Osteoblast Differentiation

Zhang, Jingru; Pang, Dan-Dan; Tong, Qiang; Liu, Xia; Su, Ding‐Feng; Dai, Sheng‐Ming

doi:10.1155/2017/5950395

Cited by 41 publications

(28 citation statements)

References 60 publications

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“…Recent efforts have focused on elucidating the mechanisms behind these effects and indicate that IL-17A stimulates receptor activator of nuclear factor-kB ligand (RANKL) expression and inhibition of Wnt signalling, thereby inhibiting osteoblast activity (figure 3). 122–128…”

Section: Role Of Il-17a In Spamentioning

confidence: 99%

The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies

et al. 2019

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Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest that immune responses mediated by interleukin 17A (IL-17A) play a pivotal role in both diseases. This is best highlighted by the significant clinical efficacy shown with inhibitors of IL-17A in treating axSpA and PsA. Nevertheless, a number of knowledge gaps exist regarding the role of IL-17A in the pathophysiology of spondyloarthritis in man, including its cellular origin, its precise role in discrete disease processes such enthesitis, bone erosion, and bone formation, and the reasons for the discrepant responses to IL-17A inhibition observed in certain other spondyloarthritis manifestations. In this review, we focus on the latest data from studies investigating the role of IL-17A in ankylosing spondylitis (AS) and PsA that build on existing and emerging scientific knowledge in the field. Key remaining research questions are also highlighted to guide future research.

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Section: Role Of Il-17a In Spamentioning

confidence: 99%

The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies

et al. 2019

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“…(14,15) Furthermore, IL17A has been reported to inhibit osteoblastogenesis. (125)(126)(127) IL17A has also been shown to induce Lcn2 in several cell types in vitro andin vivo. (124,(128)(129)(130)(131) Therefore, SFB-induced IL17A productionin thegut may stimulate hepatic LCN2 synthesis and increased circulating levels of LCN2.…”

Section: Discussionmentioning

confidence: 99%

“…IL17A signaling in stromal/osteoblastic cells critically regulates proinflammatory/pro‐osteoclastic cytokine expression, and CD4 + T H 17 cell‐derived IL17A can have catabolic actions via signaling at stromal/osteoblastic cells . Furthermore, IL17A has been reported to inhibit osteoblastogenesis . IL17A has also been shown to induce Lcn2 in several cell types in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

et al. 2020

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The commensal gut microbiota critically regulates immunomodulatory processes that influence normal skeletal growth and maturation. However, the influence of specific microbes on commensal gut microbiota osteoimmunoregulatory actions is unknown. We have shown previously that the commensal gut microbiota enhances TH17/IL17A immune response effects in marrow and liver that have procatabolic/antianabolic actions in the skeleton. Segmented filamentous bacteria (SFB), a specific commensal gut bacterium within phylum Firmicutes, potently induces TH17/IL17A‐mediated immunity. The study purpose was to delineate the influence of SFB on commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal development. Two murine models were utilized: SFB‐monoassociated mice versus germ‐free (GF) mice and specific‐pathogen‐free (SPF) mice +/− SFB. SFB colonization was validated by 16S rDNA analysis, and SFB‐induced TH17/IL17A immunity was confirmed by upregulation of Il17a in ileum and IL17A in serum. SFB‐colonized mice had an osteopenic trabecular bone phenotype, which was attributed to SFB actions suppressing osteoblastogenesis and enhancing osteoclastogenesis. Intriguingly, SFB‐colonized mice had increased expression of proinflammatory chemokines and acute‐phase reactants in the liver. Lipocalin‐2 (LCN2), an acute‐phase reactant and antimicrobial peptide, was substantially elevated in the liver and serum of SFB‐colonized mice, which supports the notion that SFB regulation of commensal gut microbiota osteoimmunomodulatory actions are mediated in part through a gut–liver–bone axis. Proinflammatory TH17 and TH1 cells were increased in liver‐draining lymph nodes of SFB‐colonized mice, which further substantiates that SFB osteoimmune‐response effects may be mediated through the liver. SFB‐induction of Il17a in the gut and Lcn2 in the liver resulted in increased circulating levels of IL17A and LCN2. Recognizing that IL17A and LCN2 support osteoclastogenesis/suppress osteoblastogenesis, SFB actions impairing postpubertal skeletal development appear to be mediated through immunomodulatory effects in both the gut and liver. This research reveals that specific microbes critically impact commensal gut microbiota immunomodulatory actions regulating normal postpubertal skeletal growth and maturation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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“…Kamiya et al [19] reported that no remarkable changes were observed in the expression of mRNA for type I collagen or ALP in osteoblasts after stimulation by IL-23, indicating that IL-23 had no direct actions on osteoblasts. We con-firmed that IL-23 had no direct effects on osteoblasts, since osteoblasts marginally express IL-23 receptors [20]. Taken together, the above data imply that IL-23 indirectly induces new bone formation at the sites of entheseal inflammation.…”

Section: Introductionmentioning

confidence: 52%

IL-23 induces the expression of pro-osteogenic factors in osteoclasts

Pang

Cai

Zhang

et al. 2020

Aktuelle Rheumatologie

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Background The mechanism for the new bone formation in ankylosing spondylitis (AS) is still unclear. Although it has been demonstrated that IL-23 plays a pivotal role in the pathophysiology of AS, IL-23 has no direct effects on osteoblasts but modulates the function of osteoclasts. Aims To explore whether IL-23 indirectly facilitates new bone formation through osteoclasts in AS, here we analyzed whether IL-23 enhances the expression levels of pro-osteogenic factors by osteoclasts. Methods Mononuclear cells were harvested from mouse bone marrow and cultured in the presence of M-CSF (50 ng/ml) and RANKL (30 ng/ml) to trigger the production of osteoclasts. Protein and mRNA expression levels of Semaphorin 4D, Ephrin B2, BMP2, BMP6, SPHK1, HtrA1 and Wnt10b were measured using Western blot and qRT-PCR. Results Primary mononuclear cells were transformed into osteoclasts with RANKL and M-CSF. The increased expression of NFATc1 and TRAP together with TRAP staining of>3 nuclei were used to identify mature osteoclasts. The mRNA expression levels of BMP2, Ephrin B2 and SPHK1 were enhanced by 1.46, 2.1 and 2.46 folds after exposure to IL-23. Confirmation of increased levels of Ephrin B2 and SPHK1 in IL-23-stimulated osteoclasts was provided by Western blot analysis. IL-23 had no effects on the expression of BMP6 or Wnt10b, or on the anti-osteogenic factors Semaphorin 4D or HtrA1. Conclusions IL-23 induces osteoclasts to express pro-osteogenic factors rather than anti-osteogenic factors, suggesting IL-23 might indirectly promote the differentiation of osteoblasts through activated osteoclasts in ankylosing spondylitis.

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Different Modulatory Effects of IL-17, IL-22, and IL-23 on Osteoblast Differentiation

Cited by 41 publications

References 60 publications

The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies

The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies

Specific Commensal Bacterium Critically Regulates Gut Microbiota Osteoimmunomodulatory Actions During Normal Postpubertal Skeletal Growth and Maturation

IL-23 induces the expression of pro-osteogenic factors in osteoclasts

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