IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation

Razawy, Wida; Alves, Celso; Koedam, Marijke; Asmawidjaja, Patrick S.; Mus, Anne‐Marie; Oukka, Mohamed; Leenen, Pieter J. M.; Visser, Jenny A.; Eerden, Bram C. J. van der; Lubberts, Erik

doi:10.1038/s41598-021-89625-2

Cited by 5 publications

(4 citation statements)

References 36 publications

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“…Razawy et al showed that 7-week-old IL-23R-/-mice have a bone mass similar to age-matched littermate control mice. In contrast, 12-week-old IL-23R-/-mice have signi cantly lower trabecular and cortical bone mass, shorter femurs, and more fragile bones [35]. Our results suggest a relationship between in ammation, alterations in the IL-23R, and the etiology of LCPD.…”

Section: Discussionmentioning

confidence: 59%

“…The IL-23R signal translation pathway has been extensively studied for its relationship with proin ammatory diseases and different pathologies that cause bone deterioration. In addition, the signaling pathway that occurs after the activity of IL-23R has plethoric effects on osteoblast and osteoclast differentiation since it can inhibit or stimulate both processes [35]. Razawy et al showed that 7-week-old IL-23R-/-mice have a bone mass similar to age-matched littermate control mice.…”

Section: Discussionmentioning

confidence: 99%

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Hemostatic markers and polymorphisms in three Mexican families with Legg-Calvé-Perthes disease.

Rodríguez-Olivas

Hernández-Zamora

Casas-Ávila

et al. 2022

Preprint

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Background: Legg-Calvé-Perthes Disease (LCPD) is a condition caused by avascular necrosis of the femoral head. Although its etiology is still not fully understood, evidence suggests heritable thrombotic and inflammatory disorders and other factors may be implicated in its onset and progress. Our objective is to describe, in the three enrolled families, the genetic, biochemical, and environmental factors that may be associated with the etiology and development of LCPD. Methods: We evaluated the following gene alterations: MTHFR, CBS, PT, FVL, FVIII, FIX, PAI-1, eNOS, IL-23R, and TNF-α, and their relationship with LCPD. Additionally, we assessed thrombophilia-associated markers (FI, FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FvW, PC, PS, AT, and homocysteine) using coagulometry methods. Results: Seven patients with LCPD and 14 healthy volunteers were enrolled. Concentrations in hemoglobin (p ≤ 0.05), fibrinogen (p ≤ 0.05), homocysteine (p =<0.05), FVIII (p≤0.05), and factor IX activity percentage (p ≤ 0.05) showed statistically significant differences. Our results show that all participants of this study present at least one mutated allele for the MTFHR (rs1801133) and IL-23R (rs1569922) polymorphisms, as well as isolated cases with other genetic variants.Conclusions: Our results show environmental elements from every family and hemostatic and inflammatory disorders may be involved in suffering and developing LCPD. Also, heritable factors could contribute to the onset of the disease. Environmental, genetic, inflammatory, and prothrombotic factors are involved in this pathology.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Hemostatic markers and polymorphisms in three Mexican families with Legg-Calvé-Perthes disease.

Rodríguez-Olivas

Hernández-Zamora

Casas-Ávila

et al. 2022

Preprint

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“…Altered expression of DLK1 [62], DBH (dopamine beta-hydroxylase) [63] and CYP17A1 [64] have previously been shown to promote depression and anxiety. DLK1 [65] and IL23R [66] were shown to participate in facilitating the osteoporosis. DBH (dopamine beta-hydroxylase) [67] has been reported to enhance CF development.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Underlying Mechanisms in Cystic Fibrosis and its Associated Complications Based on Bioinformatics Analysis of Next Generation Sequencing Data Analysis

Vastrad¹,

Vastrad²

2022

Preprint

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Cystic fibrosis (CF) is one of the inherited autosomal recessive disorders with very complicated pathogenesis. Identifying the molecular signatures and specific biomarkers of CF might provide novel clues for CF and and CF associated complications prognosis and targeted therapy. Based on the nexgeneration sequencing (NGS) dataset GSE136371 downloaded from the Gene Expression Omnibus (GEO) database, the differentially expressed genes (DEGs) between CF samples and normal controls were identified by using DESeq2 bioconductor package of R software. Gene ontology (GO) and REACTOME pathway enrichment analyses were applied for the DEGs. Then protein-protein interaction (PPI) network of these DEGs was visualized by Cytoscape with IMEx interactome database. The most significant module from the PPI network was selected for GO and pathway enrichment analysis. Subsequently, a miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed to identify hub genes, miRNAs and TFs. Finally, receiver operating characteristic curve (ROC) analysis was established to validate these hub genes. Total of 917 DEGs were identified between CF and normal control samples in GSE136371 dataset, including 479 up regulated and 438 down regulated genes. The most enriched DEGs in GO and pathway enrichment analysis were mainly associated with response to stimulus, regulation of cellular process, Neutrophil degranulation and rRNA processing. PPI network, module analysis, miRNA-hub gene regulatory network and TF-hub gene regulatory network predicted ten hub genes (FN1, UBE2D1, SRPK1, MAPK14, CEBPB, HSP90AB1, HSPA8, XRCC6, NCL and PARP1). In conclusion, the DEGs, relative pathways and hub genes identified in the present study might aid in understanding of the molecular mechanisms underlying CF and CF associated complications progression and provide potential molecular targets and biomarkers for CF and CF associated complications.

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“…Increased expression of IL-22 leads to the new periosteal bone formation through ignal transducer and activator of transcription 3 (STAT3) activation and increased expression of genes that regulate the bone formation, including the Wnt family members. In vitro studies, IL-23R-/-mice had lower cortical bone mass related to indirect effects of IL-23R on osteoblasts [9]. Also, IL-23 can reduce osteoclastogenesis via the induction of granulocytemacrophage colony-stimulating factor (GM-CSF) in murine T cells, which can reduce osteoclast formation [10].…”

Section: Early Onlinementioning

confidence: 99%

Interleukin-23 receptor gene polymorphisms in osteoporosis

Ulutaş

Cetin

Çobankara

2023

The European Research Journal

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Objectives: Osteoporosis (OP) is a usual disease with a possible genetic predisposition. IL-23 plays a role in physiological bone remodeling and regulates the activity of cells of the bone either directly or indirectly on bone-resorbing osteoclasts as well as on bone-forming osteoblasts. Recent animal and human trials have revealed the main pro-osteoclastogenic activities for the IL-23 pathway. We examined nine single nucleotide polymorphisms (SNPs) in the interleukin-23 receptor (IL-23R) in 100 OP patients and gender- and age-matched 96 healthy volunteers. The most analyzed SNPs in the recent rheumatology literature were selected. Methods: In addition to gene polymorphisms several laboratory parameters (osteocalcin, parathormone, vitamine D) were investigated. Independent Samples t-test and Mann-Whitney-U test were used to compare several demographic and clinical parameters between the groups. P-value < 0.05 was accepted to be statistically significant. Results: Having the heterozygous GA genotype of IL-23R rs1004819 and the heterozygous CT genotype of Il-23R rs7530511 significantly increase the risk of developing OP (adjusted OR: 3.51, p = 0.031 and OR: 2.41, p = 0.027, respectively). The wild homozygous GG genotype of Il-23R rs11209032 had higher osteocalcin levels compared with the mutant homozygous AA genotype (18.75 ± 9.76, p = 0.009). Conclusions: Our findings suggest that several IL-23R gene polymorphisms are seen more often in osteoporosis patients than in healthy volunteers. In addition, some SNPs were related to higher serum osteocalcin levels.

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IL-23 receptor deficiency results in lower bone mass via indirect regulation of bone formation

Cited by 5 publications

References 36 publications

Hemostatic markers and polymorphisms in three Mexican families with Legg-Calvé-Perthes disease.

Hemostatic markers and polymorphisms in three Mexican families with Legg-Calvé-Perthes disease.

Identification of Key Genes and Underlying Mechanisms in Cystic Fibrosis and its Associated Complications Based on Bioinformatics Analysis of Next Generation Sequencing Data Analysis

Interleukin-23 receptor gene polymorphisms in osteoporosis

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