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Journal of Orthopaedic Research :... Jul 2021Musculoskeletal malignancy is often accompanied by aberrant bone remodeling, leading to tumor cell invasion into skeletal tissues and causing severe pain. BMPs, FGF-2,...
Musculoskeletal malignancy is often accompanied by aberrant bone remodeling, leading to tumor cell invasion into skeletal tissues and causing severe pain. BMPs, FGF-2, and RANKL have been identified as promising regulators in physiological bone remodeling. In this study, we explored the expressional profile of BMPs, FGF-2, and RANKL in 1361 patients with 22 varieties of musculoskeletal tumors. Notably, the expression of FGF-2 and RANKL was under detected in all patients. Among BMP1 to BMP15, we found that BMP1, BMP2, BMP4, BMP5, BMP6, and BMP7 were prevalent. In comparison with normal bones, osteosarcoma highly expressed BMP1, BMP2, BMP4, and BMP7 with statistical significance. Synovial sarcoma upregulated BMP4, BMP5, and BMP7; rhabdomyosarcoma increased BMP1 and BMP4; and alveolar soft part sarcoma upregulated BMP1, BMP4, and BMP7. To visualize the BMP-oriented interactions in a bone tumor microenvironment, we have developed novel software that analyzes numerous cell-to-cell and ligand-to-receptor interactions, that is, Environmentome, delineating that osteosarcoma-secreted BMP-4 and synovial sarcoma-secreted BMP7 potently interact with osteoblasts, osteocytes, osteoclast precursors, and mature osteoclasts. Specifically, quantification analysis revealed that the relationship between osteosarcoma and mature osteoclast/precursor, BMP4-BMPR2 and BMP4-ACVR2A interactions were most potent. Regarding the association between osteosarcoma and osteocyte/osteoblast, BMP4-ACVR1 and BMP4-BMPR2 were the key interactions. In the connection between synovial sarcoma and mature osteoclast/precursor, BMP7-ACVR2A and BMP7-BMPR2 interactions were most remarkable. With regard to the cellular link between synovial sarcoma and osteocyte/osteoblast, BMP7-BMPR2 was identified as a potent interaction. In conclusion, our new outlook suggests delivering the pathological events that clinically underlie behind severe skeletal pain or fracture in musculoskeletal tumors.
Topics: Bone Morphogenetic Proteins; Bone Neoplasms; Bone Remodeling; Bone and Bones; Chondrosarcoma; Fibroblast Growth Factors; Humans; Multiple Myeloma; Muscle Neoplasms; Osteosarcoma; RANK Ligand; Tumor Microenvironment
PubMed: 33034913
DOI: 10.1002/jor.24879 -
Neurological Research Apr 2017Many studies have investigated the association between fibroblast growth factor 20(FGF20) rs12720208(C/T) polymorphism and the susceptibility of Parkinson's disease... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Many studies have investigated the association between fibroblast growth factor 20(FGF20) rs12720208(C/T) polymorphism and the susceptibility of Parkinson's disease (PD). However, published data are still controversial. Here, we performed a meta-analysis to evaluate the association of rs12720208 polymorphism with the risk of PD.
METHODS
Up to April 2016, Pubmed, EMbase, Web of science, the Chinese National Knowledge Infrastructure, and Wanfang Medicine were reviewed to identify appropriate documents. A total of seven papers involving 11 studies with 3360 PD cases and 3681 controls were included based on the strict inclusion and exclusion standards. And STATA 12.0 statistics software was used to calculate available data from each study. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated to assess the association between FGF20 rs12720208 polymorphism and PD risk.
RESULTS
When all studies were pooled into this meta-analysis, neither the minor T allele frequencies nor the genotypic distributions were different between PD cases and controls. But the subgroup analysis stratified by ethnicity showed FGF20 rs12720208 polymorphism was associated with increased risk in the allele model (T vs. C:OR = 1.167, 95% CI = 1.020-1.335) and dominant model (TT + TC vs. CC:OR = 1.156, 95% CI = 1.001-1.335) in Caucasians but not in Asians.
CONCLUSIONS
This meta-analysis indicates that rs12720208 C/T variant might be associated with PD susceptibility in Caucasians.
Topics: Animals; Fibroblast Growth Factors; Genetic Predisposition to Disease; Humans; Parkinson Disease; Polymorphism, Single Nucleotide; White People
PubMed: 28191856
DOI: 10.1080/01616412.2017.1286542 -
Cellular Signalling Jan 2022Macrophages, which are the main regulators of the tumor-associated microenvironment, play a crucial role in the progression of various tumors. The anti-inflammatory role...
Macrophages, which are the main regulators of the tumor-associated microenvironment, play a crucial role in the progression of various tumors. The anti-inflammatory role of β-catenin in macrophages has been extensively studied in recent years. However, the association between macrophages and β-catenin with regards to the development of glioma has not yet been investigated, at least to the best of our knowledge. The present study found that fibroblast growth factor 20 (FGF20), as a paracrine cytokine, was secreted by glioma cells and acted on macrophages. FGF20 treated macrophages exhibited a decreased pro-inflammatory phenotype upon LPS and IFN-γ stimulation, characterized by the decreased the level of M1 macrophage markers and the reduced production of pro-inflammatory cytokines. Mechanistic analysis revealed that FGF20 interacted with FGF receptor 1 isoform of macrophages, and subsequently increased the stability of β-catenin via phosphorylating GSK3β, which suppressed macrophage polarization to the M1-phenotype. Finally, it was found that FGF20 of glioma cells expression was upregulated by the glucocorticoids (GCs) treatment, and decreased FGF20 expression of glioma cells markedly blocked the effects of GCs on the polarization of macrophages. On the whole, the present study demonstrates that FGF20, secreted from glioma cells, participates the GCs regulated macrophage function and exerts anti-inflammatory effects during the treatment of glioma by GCs. Moreover, a molecular link was identified between glioma cells and macrophages, demonstrating that FGF20 modulates the GCs-induced dysfunction of macrophages during glioma development.
Topics: Fibroblast Growth Factors; Glioma; Humans; Macrophage Activation; Macrophages; Tumor Microenvironment; beta Catenin
PubMed: 34757019
DOI: 10.1016/j.cellsig.2021.110181 -
Human Molecular Genetics Jan 2023Asthma is a heterogeneous common respiratory disease that remains poorly understood. The established genetic associations fail to explain the high estimated...
BACKGROUND
Asthma is a heterogeneous common respiratory disease that remains poorly understood. The established genetic associations fail to explain the high estimated heritability, and the prevalence of asthma differs between populations and geographic regions. Robust association analyses incorporating different genetic ancestries and whole-genome sequencing data may identify novel genetic associations.
METHODS
We performed family-based genome-wide association analyses of childhood-onset asthma based on whole-genome sequencing (WGS) data for the 'The Genetic Epidemiology of Asthma in Costa Rica' study (GACRS) and the Childhood Asthma Management Program (CAMP). Based on parent-child trios with children diagnosed with asthma, we performed a single variant analysis using an additive and a recessive genetic model and a region-based association analysis of low-frequency and rare variants.
RESULTS
Based on 1180 asthmatic trios (894 GACRS trios and 286 CAMP trios, a total of 3540 samples with WGS data), we identified three novel genetic loci associated with childhood-onset asthma: rs4832738 on 4p14 ($P=1.72\ast{10}^{-9}$, recessive model), rs1581479 on 8p22 ($P=1.47\ast{10}^{-8}$, additive model) and rs73367537 on 10q26 ($P=1.21\ast{10}^{-8}$, additive model in GACRS only). Integrative analyses suggested potential novel candidate genes underlying these associations: PGM2 on 4p14 and FGF20 on 8p22.
CONCLUSION
Our family-based whole-genome sequencing analysis identified three novel genetic loci for childhood-onset asthma. Gene expression data and integrative analyses point to PGM2 on 4p14 and FGF20 on 8p22 as linked genes. Furthermore, region-based analyses suggest independent potential low-frequency/rare variant associations on 8p22. Follow-up analyses are needed to understand the functional mechanisms and generalizability of these associations.
Topics: Humans; Genome-Wide Association Study; Genetic Predisposition to Disease; Asthma; Genetic Loci; Whole Genome Sequencing; Polymorphism, Single Nucleotide; Fibroblast Growth Factors
PubMed: 36255742
DOI: 10.1093/hmg/ddac258 -
Bulletin Du Cancer Apr 2022This study aims to elucidate the characteristic and expression level of miR-1226 in non-small cell lung cancer (NSCLC) tissue samples and cell lines, and its potential...
OBJECTIVE
This study aims to elucidate the characteristic and expression level of miR-1226 in non-small cell lung cancer (NSCLC) tissue samples and cell lines, and its potential influence on the malignant progression of NSCLC.
METHODS
The expression level of miR-1226 in tumor tissue and paracancerous tissue of NSCLC patients was detected by qRT-PCR. The influences on clinical features of NSCLC patients were analyzed. The proliferation and metastasis ability in H1299 and SPC-A1 cells were examined by CCK-8 and Transwell assay, respectively. Subsequently, the binding relationship between miR-1226 and FGF2 was verified by dual-luciferase reporter assay. The upstream regulatory factor ASCL1 was identified through database prediction, and the co-regulation on NSCLC cell lines was explored via rescue experiments.
RESULTS
miR-1226 was down-regulated in NSCLC tissue samples and cell lines, which suggested that miR-1226 was associated with tumor stage and lymph node metastasis. The transfection of miR-1226 mimic inhibited the proliferation and migration in H1299 and SPC-A1 cells. In addition, the overexpression of miR-1226 suppressed tumor growth in vivo. FGF2 was the downstream target binding miR-1226, which was up-regulated in NSCLC tissue samples. Moreover, ASCL1 was found to be a potential regulator of miR-1226. Finally, the tumor suppressive effect of miR-1226 was reversed by its downstream FGF2 and upstream factor ASCL1.
CONCLUSIONS
miR-1226, which was regulated by ASCL1, inhibited tumor growth and migration by targeting FGF2, indicating that the ASCL1/miR-1226/FGF2 axis could be a potential therapeutic target for NSCLC.
Topics: Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Movement; Cell Proliferation; Fibroblast Growth Factor 2; Fibroblast Growth Factors; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; MicroRNAs
PubMed: 35164915
DOI: 10.1016/j.bulcan.2021.11.017 -
Brain : a Journal of Neurology Mar 2021Genome-wide association studies (GWAS) have identified numerous loci associated with Parkinson's disease. The specific genes and variants that drive the associations...
Genome-wide association studies (GWAS) have identified numerous loci associated with Parkinson's disease. The specific genes and variants that drive the associations within the vast majority of these loci are unknown. We aimed to perform a comprehensive analysis of selected genes to determine the potential role of rare and common genetic variants within these loci. We fully sequenced 32 genes from 25 loci previously associated with Parkinson's disease in 2657 patients and 3647 controls from three cohorts. Capture was done using molecular inversion probes targeting the exons, exon-intron boundaries and untranslated regions (UTRs) of the genes of interest, followed by sequencing. Quality control was performed to include only high-quality variants. We examined the role of rare variants (minor allele frequency < 0.01) using optimized sequence Kernel association tests. The association of common variants was estimated using regression models adjusted for age, sex and ethnicity as required in each cohort, followed by a meta-analysis. After Bonferroni correction, we identified a burden of rare variants in SYT11, FGF20 and GCH1 associated with Parkinson's disease. Nominal associations were identified in 21 additional genes. Previous reports suggested that the SYT11 GWAS association is driven by variants in the nearby GBA gene. However, the association of SYT11 was mainly driven by a rare 3' UTR variant (rs945006601) and was independent of GBA variants (P = 5.23 × 10-5 after exclusion of all GBA variant carriers). The association of FGF20 was driven by a rare 5' UTR variant (rs1034608171) located in the promoter region. The previously reported association of GCH1 with Parkinson's disease is driven by rare non-synonymous variants, some of which are known to cause dopamine-responsive dystonia. We also identified two LRRK2 variants, p.Arg793Met and p.Gln1353Lys, in 10 and eight controls, respectively, but not in patients. We identified common variants associated with Parkinson's disease in MAPT, TMEM175, BST1, SNCA and GPNMB, which are all in strong linkage disequilibrium with known GWAS hits in their respective loci. A common coding PM20D1 variant, p.Ile149Val, was nominally associated with reduced risk of Parkinson's disease (odds ratio 0.73, 95% confidence interval 0.60-0.89, P = 1.161 × 10-3). This variant is not in linkage disequilibrium with the top GWAS hits within this locus and may represent a novel association. These results further demonstrate the importance of fine mapping of GWAS loci, and suggest that SYT11, FGF20, and potentially PM20D1, BST1 and GPNMB should be considered for future studies as possible Parkinson's disease-related genes.
Topics: Adult; Aged; Female; Fibroblast Growth Factors; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; Parkinson Disease; Polymorphism, Single Nucleotide; Synaptotagmins
PubMed: 33349842
DOI: 10.1093/brain/awaa401 -
Genes Apr 2021Parkinson's disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one... (Meta-Analysis)
Meta-Analysis
Parkinson's disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one of the risk loci located near the gene that has been implicated in PD. The variation of in the 3' untranslated region was shown to increase α-synuclein expression. We examined the association of rs591323 with the risk of PD in a Taiwanese population and conducted a meta-analysis, including our study and two other studies from China, to further confirm the role of this SNP in Taiwanese/Chinese populations. A total of 586 patients with PD and 586 health controls (HCs) were included in our study. We found that the minor allele (A) and the AA + GA genotype under the dominant model are significantly less frequent in PD than in controls. The meta-analysis consisted of 1950 patients with PD and 2073 healthy controls from three studies. There was significant association between rs591323 and the risk of PD in the additive (Z = -3.96; < 0.0001) and the dominant models (Z = -4.01; < 0.0001). Our study results and the meta-analysis support the possible protective role of the rs591323 A allele in PD in Taiwanese/Chinese populations.
Topics: China; Fibroblast Growth Factors; Humans; Parkinson Disease; Polymorphism, Single Nucleotide; Taiwan
PubMed: 33947140
DOI: 10.3390/genes12050674 -
The British Journal of Oral &... Jan 2021Our purpose was to measure the temporomandibular joint (TMJ) synovial fluid (SF) levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2...
Our purpose was to measure the temporomandibular joint (TMJ) synovial fluid (SF) levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) before and after intra-articular injection of hyaluronic acid (HA) and to investigate the possible mechanism involved in the therapeutic value of HA. We analysed the synovial fluid of 30 patients with unilateral internal derangement (ID) or osteoarthritis (OA) of the TMJ (confirmed by magnetic resonance imaging and cone-beam computed tomography) and recorded clinical signs and symptoms including maximal mouth opening, subjective joint pain, and joint noise at the patient's each visit. All clinical signs significantly improved after injection of HA, and there was no significant difference between ID and OA groups. In synovial fluid parameters, the concentration of VEGF was significantly higher before treatment with HA than after treatment, but there was no significant difference in the concentration of FGF-2 between before and after treatment. The study findings suggest intra-articular injection of HA may reduce the synovitis and improve the internal state of the TMJ in a short period.
Topics: Fibroblast Growth Factor 2; Fibroblast Growth Factors; Humans; Hyaluronic Acid; Injections, Intra-Articular; Synovial Fluid; Temporomandibular Joint Disorders; Vascular Endothelial Growth Factor A
PubMed: 32727671
DOI: 10.1016/j.bjoms.2020.07.013 -
Neuroscience Letters May 2018Parkinson's disease (PD) is the second most common neurodegenerative disease and has a complex etiology. Single nucleotide polymorphisms in the 3'-untranslated region of...
BACKGROUND
Parkinson's disease (PD) is the second most common neurodegenerative disease and has a complex etiology. Single nucleotide polymorphisms in the 3'-untranslated region of Fibroblast growth factor 20 (FGF 20) have been reported to be associated with PD; however, the results are controversial. Although FGF20 enhances the survival of dopaminergic neurons, it may also result in PD susceptibility by altering alpha-synuclein expression.
MATERIALS AND METHODS
To identify and characterize genetic risk variants in FGF 20 in Eastern Indian PD patients, 2 SNPs of FGF 20 (rs1721100 and rs2720208) were genotyped in 336 PD cases and 313 ethnically matched controls by PCR-RFLP.
RESULTS
We observed statistically significant differences in genotypic and allelic frequencies of rs1721100 between PD cases and controls but not for rs12720208. Haplotype G-C showed a significant protective effect against PD. A functional assay revealed that the risk allele C at rs1721100 has little or no effect on relative luciferase activity from a reporter construct in the presence of miR-3189-3p, whereas allele G results in significant dose-dependent reduction.
CONCLUSION
Our results suggest that FGF 20 is a susceptibility gene for PD in Eastern Indians.
Topics: 3' Untranslated Regions; Adult; Female; Fibroblast Growth Factors; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Haplotypes; Humans; India; Male; Middle Aged; Parkinson Disease; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 29604408
DOI: 10.1016/j.neulet.2018.03.059 -
Neurological Sciences : Official... May 2022While many studies have investigated the associations between fibroblast growth factor 20 (FGF20) rs1721100 (C/G) and rs12720208 (C/T) polymorphisms and susceptibility... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
While many studies have investigated the associations between fibroblast growth factor 20 (FGF20) rs1721100 (C/G) and rs12720208 (C/T) polymorphisms and susceptibility to Parkinson's disease (PD), their results are controversial. Our present meta-analysis estimated the overall association between FGF20 rs1721100 and rs12720208 polymorphisms and the risk of sporadic PD.
METHODS
We performed a comprehensive literature search of the PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, and Wanfang Medicine electronic databases, which was updated in April 2021. Based on strict inclusion and exclusion criteria, the analysis included a total of 10 papers involving 14 studies with 5262 cases of PD and 6075 controls. Review Manager 5.4 software was used to assess the available data from each study. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the association between the FGF20 rs1721100 and rs12720208 polymorphisms and sporadic PD risk.
RESULTS
Our results showed that the FGF20 rs1721100 G allele frequency and genotype distribution did not differ between PD patients and controls. Similarly, the FGF20 rs12720208 T allele frequency and genotype distribution did not differ significantly between the two groups. A subgroup analysis of Asian and Caucasian populations also showed the same results.
CONCLUSIONS
The results of this meta-analysis indicated that neither the rs1721100 C/G nor the rs12720208 C/T variants were associated with sporadic PD susceptibility.
Topics: Asian People; Fibroblast Growth Factors; Genetic Predisposition to Disease; Humans; Parkinson Disease; Polymorphism, Single Nucleotide
PubMed: 34845561
DOI: 10.1007/s10072-021-05754-6