Editorial: Flt3 ligand—friend or foe?

Voronov, Irina; Manolson, Morris F.

doi:10.1189/jlb.3ce0915-445rr

Cited by 5 publications

(4 citation statements)

References 12 publications

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“…FLT3LG studies in the biomedical literature are more related to leukaemia than musculoskeletal diseases [ 60 ]. The role of this cytokine in bone joints is debated and has mainly been described in rheumatoid arthritis, where it is considered to be a negative regulator of osteoclastogenesis and a bone-protective factor [ 61 ]. This may explain the weak association with fracture risk seen in our study ( R 2 = − 0.356).…”

Section: Discussionmentioning

confidence: 99%

Effect of immunology biomarkers associated with hip fracture and fracture risk in older adults

Cedeno-Veloz,

Lozano-Vicario,

Zambom-Ferraresi

et al. 2023

Immun Ageing

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Osteoporosis is a skeletal disease that can increase the risk of fractures, leading to adverse health and socioeconomic consequences. However, current clinical methods have limitations in accurately estimating fracture risk, particularly in older adults. Thus, new technologies are necessary to improve the accuracy of fracture risk estimation. In this observational study, we aimed to explore the association between serum cytokines and hip fracture status in older adults, and their associations with fracture risk using the FRAX reference tool. We investigated the use of a proximity extension assay (PEA) with Olink. We compared the characteristics of the population, functional status and detailed body composition (determined using densitometry) between groups. We enrolled 40 participants, including 20 with hip fracture and 20 without fracture, and studied 46 cytokines in their serum. After conducting a score plot and two unpaired t-tests using the Benjamini-Hochberg method, we found that Interleukin 6 (IL-6), Lymphotoxin-alpha (LT-α), Fms-related tyrosine kinase 3 ligand (FLT3LG), Colony stimulating factor 1 (CSF1), and Chemokine (C-C motif) ligand 7 (CCL7) were significantly different between fracture and non-fracture patients (p < 0.05). IL-6 had a moderate correlation with FRAX (R2 = 0.409, p < 0.001), while CSF1 and CCL7 had weak correlations with FRAX. LT-α and FLT3LG exhibited a negative correlation with the risk of fracture. Our results suggest that targeted proteomic tools have the capability to identify differentially regulated proteins and may serve as potential markers for estimating fracture risk. However, longitudinal studies will be necessary to validate these results and determine the temporal patterns of changes in cytokine profiles.

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Section: Discussionmentioning

confidence: 99%

Effect of immunology biomarkers associated with hip fracture and fracture risk in older adults

Cedeno-Veloz,

Lozano-Vicario,

Zambom-Ferraresi

et al. 2023

Immun Ageing

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“…By promoting transcription of interferon regulatory factor 8 (IRF8) and sustaining a balance between protective regulatory T cells and pathogenic T helper 17, FL may serve as a negative regulator of OC development. Thus, Voronov and co-workers concluded a pro-and anti-resorptive function of FL [21]. In FLT3 ITD-positive AML samples, a trend towards downregulation of FL was observed.…”

Section: Fl Induced Flt3 Signalling Regulates Cytokinesmentioning

confidence: 92%

“…Local knee exposure to FL aggravated arthritis in mice [18]. Thus, the above findings suggest that the FL-FLT3 signalling axis has proosteoclastogenic properties [21]. The receptor tyrosine kinase FLT3 plays a role in proliferation and differentiation of B-cell progenitors, myelomonocytic and dendritic cells, as well as in the maintenance of pluripotent haematopoietic stem cells [22].…”

Section: Introductionmentioning

confidence: 99%

Aberrant Bone Homeostasis in AML Is Associated with Activated Oncogenic FLT3-Dependent Cytokine Networks

Bär

Ast

Meyer

et al. 2020

Cells

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Acute myeloid leukaemia (AML) is a haematopoietic malignancy caused by a combination of genetic and epigenetic lesions. Activation of the oncoprotein FLT3 ITD (Fms-like tyrosine kinase with internal tandem duplications) represents a key driver mutation in 25–30% of AML patients. FLT3 is a class III receptor tyrosine kinase, which plays a role in cell survival, proliferation, and differentiation of haematopoietic progenitors of lymphoid and myeloid lineages. Mutant FLT3 ITD results in an altered signalling quality, which causes cell transformation. Recent evidence indicates an effect of FLT3 ITD on bone homeostasis in addition to haematological aberrations. Using gene expression data repositories of FLT3 ITD-positive AML patients, we identified activated cytokine networks that affect the formation of the haematopoietic niche by controlling osteoclastogenesis and osteoblast functions. In addition, aberrant oncogenic FLT3 signalling of osteogenesis-specific cytokines affects survival of AML patients and may be used for prognosis. Thus, these data highlight the intimate crosstalk between leukaemic and osteogenic cells within the osteohaematopoietic niche.

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“… Has proinflammatory and proosteoclastogenic properties contributing to bone loss (Voronov & Manolson, 2016). …”

Section: Mesenchymal Stem Cells Therapy: a Stimuli To Attenuate Inflammageingmentioning

confidence: 99%

The potential role of mesenchymal stem cells in modulating antiageing process

Govindasamy¹,

Rajendran²,

Lee³

et al. 2021

Cell Biology International

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Ageing and age‐related diseases share some basic origin that largely converges on inflammation. Precisely, it boils down to a common pathway characterised by the appearance of a fair amount of proinflammatory cytokines known as inflammageing. Among the proposed treatment for antiageing, MSCs gained attention in recent years. Since mesenchymal stem cells (MSCs) can differentiate itself into a myriad of terminal cells, previously it was believed that these cells migrate to the site of injury and perform their therapeutic effect. However, with the more recent discovery of huge amounts of paracrine factors secreted by MSCs, it is now widely accepted that these cells do not engraft upon transplantation but rather unveil their benefits through excretion of bioactive molecules namely those involved in inflammatory and immunomodulatory activities. Conversely, the true function of these paracrine changes has not been thoroughly investigated all these years. Hence, this review will describe in detail on ways MSCs may capitalize its paracrine properties in modulating antiageing process. Through a comprehensive literature search various elements in the antiageing process, we aim to provide a novel treatment perspective of MSCs in antiageing related clinical conditions.

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Editorial: Flt3 ligand—friend or foe?

Abstract: Discussion on the contradictory evidence of both pro‐ and anti‐resorptive properties of Fms‐like Flt3L in RA.

Cited by 5 publications

References 12 publications

Effect of immunology biomarkers associated with hip fracture and fracture risk in older adults

Effect of immunology biomarkers associated with hip fracture and fracture risk in older adults

Aberrant Bone Homeostasis in AML Is Associated with Activated Oncogenic FLT3-Dependent Cytokine Networks

The potential role of mesenchymal stem cells in modulating antiageing process

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