Microtopography of Immune Cells in Osteoporosis and Bone Lesions by Endocrine Disruptors

Toni, Roberto; Conza, Giusy Di; Barbaro, Fulvio; Zini, Nicoletta; Consolini, Elia; Dallatana, D.; Antoniel, Manuela; Quarantini, Enrico; Quarantini, Marco; Maioli, Sara; Bruni, Celeste Angela; Panseri, Silvia; Sprio, Simone; Sandri, Monica; Tampieri, Anna

doi:10.3389/fimmu.2020.01737

Cited by 28 publications

(21 citation statements)

References 66 publications

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Section: Discussionmentioning

confidence: 50%

“…Out of the 8 predicted target genes of DEmiRs, FOXO4 yielded the largest AUC within the LASSO model and among the target genes of miRNAs, so we hypothesize that it may be a key gene in PMOP. Immune cells are involved in osteoporosis, 49 and our study found that among the 24 immune cell types, DCs and T cells are highly expressed in 50,51 Moreover, the homeostasis of T cells can cause inflammation, resulting in substantial bone resorption and loss of bone mineral density. 52 While FOXO4 has also been studied in bone metabolism, it has mostly been reported in the context of cancers, including leukemia, neuroblastoma, as well as cervical, colorectal, pancreatic and lung cancers.…”

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confidence: 64%

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FOXO4 May Be a Biomarker of Postmenopausal Osteoporosis

Yang¹,

He²,

Hu³

et al. 2022

IJGM

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Purpose Postmenopausal osteoporosis (PMOP) is a common and debilitating chronic disease, but it has just no cure options. The objective of this study was to identify genes associated with osteoporosis and reveal potential therapeutic targets. Methods Expression profiles from GSE13850 and GSE56815 datasets were combined for differential expression analysis. Extraction of intersecting genes from the combined datasets and the differentially expressed genes in GSE56814 were performed to construct a multi-scale embedded gene co-expression network analysis (MEGENA) to obtain module genes. Module genes with an area under the receiver operating characteristic curve (AUC) >0.60 were chosen to construct the least absolute shrinkage and selection operator (LASSO) model to obtain feature genes. A regulated network was constructed using differentially expressed micro-RNAs (miRNAs) in GSE74209 and feature genes. Finally, key genetic pathways and pathways of the Kyoto Encyclopedia of Genes and Genomes were identified and explored. Results The commonly identified differentially expressed genes involve oxidative phosphorylation and caffeine metabolism. We identified 66 modules with 2354 module genes based on MEGENA. CARD8, FOXO4, IL1R2, MPHOSPH6, MPRIP, MYOM1, PRR5L and YIPF4 were identified as feature genes by the LASSO model. Furthermore, predicted miRNA target genes included 8 genes associated with PMOP. The largest AUC was observed for FOXO4, which was found at the nexus of feature genes and miRNA-regulated genes and which correlated with the upregulation of dendritic cells. Moreover, FOXO4 was found to be involved in ABC transporters, as well as cocaine and nicotine addiction. Conclusion FOXO4 may serve as potential biomarker and therapeutic target for PMOP.

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Section: Discussionmentioning

confidence: 50%

mentioning

confidence: 64%

FOXO4 May Be a Biomarker of Postmenopausal Osteoporosis

Yang¹,

He²,

Hu³

et al. 2022

IJGM

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“…Bone disease is highly prevalent among patients with chronic kidney disease (Stehman-Breen, 2004). Previous studies showed immune system and immune factors play important regulatory roles in occurrence of osteoporosis (Toni et al, 2020;Zhao et al, 2018). As…”

Section: Discussionmentioning

confidence: 97%

“…Bone disease is highly prevalent among patients with chronic kidney disease (Stehman‐Breen, 2004). Previous studies showed immune system and immune factors play important regulatory roles in occurrence of osteoporosis (Toni et al., 2020; Zhao et al., 2018). As injected AMSCs in Bmi‐1 −/− mice migrated to different organs, including kidney, spleen, thymus, and improved the function of located organs.…”

Section: Discussionmentioning

confidence: 99%

Amniotic membrane mesenchymal stem cells‐based therapy improves Bmi‐1‐deficient mandible osteoporosis through stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption

Yin

Wang

Xie

et al. 2022

J Tissue Eng Regen Med

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Mandible osteoporosis with age is characterized by greater fragility and accompanied with abnormal oral function. Mesenchymal stem cell transplantation can ameliorate osteoporosis. Bmi‐1 is a transcriptional repressor which is an important regulator of cell cycle, stem cells self‐renewal, and cell senescence. Here, we use a new kind of membrane mesenchymal stem cells (MSCs), amniotic membrane mesenchymal stem cells (AMSCs), to explore therapeutic effects on Bmi‐1‐deficient caused mandible osteoporosis. Phenotypes of mandibles from 5‐week‐old Bmi‐1‐deficient mice with AMSCs‐based therapy were compared with age‐matched Bmi‐1‐deficient mandibles without AMSCs‐based therapy and wild‐type mice. Bmi‐1‐deficient mice without AMSCs‐based therapy displayed mandible osteoporosis accompanied with the rising senescence‐associated molecules and imbalance redox homeostasis. Results showed that the alveolar bone volume, cortical thickness, type I collagen and osteocalcin immunopositive areas, mRNA expression levels of alkaline phosphatase, superoxide dismutase, gluathione reductase, and protein expression level of Runx2 were all reduced significantly in Bmi‐1−/− mandibles. Protein levels of PPARγ, p16, p21, p53, and redox gene levels of Bnip3l, Cdo1, Duox1, and Duox2 were up‐regulated in mandibles from vehicle‐transplanted Bmi‐1−/− mice. Also, osteoclasts were activated in Bmi‐1−/− alveolar bone. Transplanted AMSCs migrated into mandibles and improved all the parameters in Bmi‐1−/− mandibles with AMSCs‐based therapy. These findings indicate that AMSCs‐based therapy could rescue mandible osteoporosis induced by Bmi‐1 deficiency through stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption. Our findings implied that AMSCs‐based therapy had preventative and therapeutic potential for mandible osteoporosis.

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“…However, the literature remains nuanced and PAR2-mediated M2 skewing has also been reported in response to Mycobacterium tuberculosis antigen [104]. By regulating the differentiation and activation of macrophages which are functionally related to bone remodeling, FXa and indirectly FVIII might be involved in bone diseases [105] (Figure 1). Questions regarding the direct or indirect impact of FVIII and the molecular complexes related to FVIII in macrophage differentiation and their role in osteoimmunology remain open and will require new clinical investigations including adequate control groups.…”

Section: Can the Polarization Of Macrophages The Neovascularization A...mentioning

confidence: 99%

FVIII at the crossroad of coagulation, bone and immune biology: Emerging evidence of biological activities beyond hemostasis

Cadé

Muñoz-García

Babuty

et al. 2022

Drug Discovery Today

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Microtopography of Immune Cells in Osteoporosis and Bone Lesions by Endocrine Disruptors

Cited by 28 publications

References 66 publications

FOXO4 May Be a Biomarker of Postmenopausal Osteoporosis

FOXO4 May Be a Biomarker of Postmenopausal Osteoporosis

Amniotic membrane mesenchymal stem cells‐based therapy improves Bmi‐1‐deficient mandible osteoporosis through stimulating osteoblastic bone formation and inhibiting osteoclastic bone resorption

FVIII at the crossroad of coagulation, bone and immune biology: Emerging evidence of biological activities beyond hemostasis

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