The osteogenic capacity and lncRNA/mRNA expression profile of periosteal-derived mesenchymal stem cells of congenital pseudarthrosis of the tibia
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ABSTRACT:
PROVIDER: PRJNA822819 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18590336_1.fastq.gz | Fastqsanger.gz | |||
| SRR18590336_2.fastq.gz | Fastqsanger.gz | |||
| SRR18590337_1.fastq.gz | Fastqsanger.gz | |||
| SRR18590337_2.fastq.gz | Fastqsanger.gz | |||
| SRR18590338_1.fastq.gz | Fastqsanger.gz |
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Project description:Congenital pseudarthrosis of the tibia (CPT) is a severe pediatric disorder affecting children. CPT is characterized by tibial bowing at birth leading to spontaneous fracture and fibrous non-union. Our study showed the presence of biallelic inactivation of the NF1 gene in the periosteum and in periosteal skeletal/stem progenitor cells (pSSPCs) at the pseudarthrosis site.
2024-07-24 | GSE234071 | GEO
Project description:Purpose: Congenital pseudarthrosis of the tibia (CPT) is an uncommon disease. The biological properties, molecular patterns, and regulatory mechanisms of periosteal-derived mesenchymal stromal cells (PDMSCs) remain unclear. Methods: PDMSCs were separated from patients with either CPT or control donors. The purity of stem cells was determined by flow cytometry. Using osteogenic induction culture and Co-culture THP1-derived macrophage and PDMSCs, the osteogenic and osteoclastic activities were determined by histological examination and western blot analysis. The differential expression of lncRNA/mRNA was analyzed through RNA-Seq. Results: The proportion of CD31 and CD34 positive cells were less than 1.5%, while CD44 and CD90 positive cells were higher than 95% in PDMSCs. After osteogenic differentiation induction, the calcium nodule formation and osteogenic protein indicators levels were lower in CPT-PDMSCs. Co-culture THP1-derived macrophage and PDMSCs, after osteoclast differentiation induction, dissolved hydroxyapatite plate activity, osteoclastic protein indicators levels of co-culture with CPT PDMSCs were shown to be higher than control. RNA-seq results revealed 822 differentially expressed mRNAs and 194 differentially expressed lncRNAs, respectively. Functional analysis showed that differentially expressed lncRNAs involved in tryptophan metabolism, steroid biosynthesis, and so on. Based on differential mRNAs and lncRNAs, we conducted correlation analysis of their cis regulation, and the results showed that 27 mRNAs were cis regulated with 24 lncRNAs, a total of 30 cis-regulated combinations. Conclusion: CPT-PDMSCs has weak osteogenesis ability, but stronger ability to promotes osteoclast differentiation, we found that certain lncRNAs and mRNAs were differentially expressed in CPT-PDMSCs which have important roles in regulated osteogenesis and osteoclast differentiation.
2022-09-20 | GSE200069 | GEO
Project description:RNAseq of periosteal stem/progenitor cells from patients with congenital pseudarthrosis of the tibia
| PRJNA979261 | ENA
Project description:Congenital pseudarthrosis of the tibia (CPT) is a severe pediatric disorder affecting children. CPT is characterized by tibial bowing at birth leading to spontaneous fracture and fibrous non-union. Our study showed the presence of biallelic inactivation of the NF1 gene in the periosteum at the pseudarthrosis site. To understand the impact of NF1 mutation on the periosteum, we performed single nuclei RNAseq of pathological periosteum collected from the pseudarthrosis site and of non-pathological periosteum collected from the iliac crest of 3 CPT patients.
2024-07-24 | GSE232516 | GEO
Project description:Congenital pseudarthrosis of the tibia (CPT) is a refractory condition characterized by the decreased osteogenic ability in tibial pseudarthrosis repair. Periosteal mesenchymal stem cells (PMSCs) are multipotent cells involved in bone formation regulation. However, the mechanisms underlying its role in CPT remain unclear. In this study, we observed downregulation of circ_0000888 and pleiotrophin (PTN), as well as upregulation of miR-338-3p in CPT derived PMSCs (CPT-dPMSCs). Our results demonstrated that circ_0000888 and PTN likely enhanced the viability, proliferation, and osteogenic ability of PMSCs, while miR-338-3p had the opposite effect. Further analysis confirmed the regulatory relationship circ_0000888 suppressed the activity of miR-338-3p and upregulated the expression of its downstream target PTN by binding to miR-338-3p, consequently promoting the viability and osteogenic differentiation ability of CPT-dPMSCs. Our findings unveil an unexpected link between circ_0000888/miR-338-3p/PTN in promoting osteogenic ability and indicate the potential pathogenic mechanisms of CPT.
| S-EPMC10551655 | biostudies-literature
Project description:Single nuclei RNAseq of the human periosteum from patients with congenital pseudarthrosis of the tibia
| PRJNA972648 | ENA
Project description:BackgroundCongenital pseudarthrosis of the tibia (CPT) is a refractory and rare disease. Because of its extremely low incidence, little is known about its clinical features. In this retrospective study, we aim to analyze the clinical characteristics of patients with CPT.Materials and methodsThis is a retrospective study of children with CPT identified by the radiological review. Investigations of CPT included general conditions, the characteristics of CPT, treatment methods, and surgical complications.ResultsWe collected 514 CPT cases from March 1999 to March 2020 in our hospital, such as 317 (61.67%) boys, 197 (38.33%) girls; 330 (62.86%) in Crawford IV; 510 (97.14%) in mid and distal 1/3 tibia; 481 (93.58%) in less than 3 years at onset age; 297 (57.78%) in less than 3 years at the first outpatient visit. The most common post-operative complication was ankle valgus (101, 39.60%), followed by limb length discrepancy (91, 35.69%), refracture (38, 14.90%), osteomyelitis (15, 5.88%), and removal of internal fixation (10, 3.93%).ConclusionsCPT with a higher incidence of Crawford IV frequently occurs in boys and the middle or distal part of the tibia; most patients have the onset age and first outpatient visit before 3 years; the major surgical complications are ankle valgus and limb length discrepancy.
| S-EPMC9452726 | biostudies-literature
Project description:BackgroundThis study evaluated the correlation of preoperative concurrent fibular pseudarthrosis with the risk of ankle valgus deformity in patients with congenital pseudarthrosis of the tibia (CPT) who underwent successful surgical treatment.MethodThe children with CPT who were treated at our institution between 1 January 2013 and 31 December 2020 were retrospectively reviewed. The independent variable was preoperative concurrent fibular pseudarthrosis, and the dependent variable was postoperative ankle valgus. Multivariable logistic regression analysis was performed after adjusting for variables that might affect the risk of ankle valgus. Subgroup analyses with stratified multivariable logistic regression models were used to assess this association.ResultsOf the 319 children who underwent successful surgical treatment, 140 (43.89%) developed ankle valgus deformity. Moreover, 104 (50.24%) of 207 patients with preoperative concurrent fibular pseudarthrosis developed an ankle valgus deformity compared with 36 (32.14%) of 112 patients without preoperative concurrent fibular pseudarthrosis (p=0.002). After adjusting for sex, body mass index, fracture age, age of patient undergoing surgery, surgery method, type 1 neurofibromatosis (NF-1), limb-length discrepancy (LLD), CPT location and fibular cystic change, patients with concurrent fibular pseudarthrosis presented a higher risk of ankle valgus than those without concurrent fibular pseudarthrosis (OR 2.326, 95% CI 1.345 to 4.022). This risk further increased with CPT location at the distal one-third of the tibia (OR 2.195, 95% CI 1.154 to 4.175), age <3 years of patient undergoing surgery (OR 2.485, 95% CI 1.188 to 5.200), LLD <2 cm (OR 2.478, 95% CI 1.225 to 5.015) and occurrence of NF-1 disorder (OR 2.836, 95% CI 1.517 to 5.303).ConclusionOur results indicate that patients with CPT and preoperative concurrent fibular pseudarthrosis have a significantly increased risk of ankle valgus compared with those without preoperative concurrent fibular pseudarthrosis, particularly in those with CPT location at the distal third, age <3 years at surgery, LLD <2 cm and NF-1 disorder.
| S-EPMC9972442 | biostudies-literature
Project description:Neurofibromatosis Type 1 (NF1) is a tumor predisposition syndrome with pleiotropic somatic manifestations, including formation of bone pseudarthrosis after fracture. The pathogenesis of NF1 pseudarthroses remains unclear, though defects in osteogenesis have been posited. Here, we applied time-series single-cell RNA-sequencing (scRNAseq) to patient-matched control and pseudarthrosis-derived primary bone mesenchymal stromal cells (MSCs). We show that osteogenesis occurs in NF1-/- MSCs. In contrast, expression of genetic pathways associated with skeletal mineralization were reduced in NF1-/- cells compared to co-cultured NF1+/- fracture-derived cells.
2022-12-13 | GSE196652 | GEO
Project description:Background: To analyze the lncRNA-mRNA differential expression and co-expression network of periosteal stem cells (PSCs) from congenital pseudarthrosis of the tibia (CPT) and normal patients, and to explore the role of key lncRNAs. Methods: Differentially expressed lncRNAs and mRNAs in PSCs were obtained by sequencing, and biological functions of differentially expressed mRNAs were detected by gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway and protein -protein interaction (PPI) analysis. The co-expression network of lncRNA-mRNA was constructed by correlation analysis of differentially expressed lncRNAs and mRNAs, and the key lncRNAs were screened according to the connectivity degree. After that, the cis-regulated target genes of differential expressed lncRNAs and mRNAs were predicted. Results: A total of 194 differentially expressed lncRNAs were identified, including 73 upregulated and 121 downregulated genes. A total of 822 differentially expressed mRNAs were identified, including 311 upregulated and 511 downregulated genes. GO, KEGG and PPI enrichment analysis showed that the regulatory function of differentially expressed mRNAs were mainly gathered in skeletal system development and tissue morphogenesis. The co-expression network with 226 nodes and 3,390 edges was constructed based on correlation analysis. A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147 and AC103702, were screened according to connectivity degree. Prediction of target genes indicated that FAM227B-FGF7 and AC103702-HOXB4/5/6 may play an important role in the pathogenesis of CPT. Conclusion: A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147, and AC103702, occupy the core position in the co-expression network, suggesting that these lncRNAs and their target genes may play an important role in the pathogenesis of CPT.
| S-EPMC9939773 | biostudies-literature