The neurotrophin receptor p75NTR orchestrates chondrogenesis and mechano-adaptation to preserve temporomandibular joint growth and homeostasis (scRNA seq analysis)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE313304 | GEO | 2026/09/17
REPOSITORIES: GEO
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Project description:Neurotrophins (NTs) promotes angiogenesis and EC survival, via tropomyosin kinase trkA and trkB receptors. A different p75NTR receptor of NTs, which belongs to the TNF-alfa receptor superfamily, is not or scarcely expressed by endothelial cells (EC) and endothelial progenitor cells (EPC) under basal conditions. Both diabetes and muscular ischemia induce p75NTR in capillary EC. In this study, by gene transfer, we forced the expression of p75NTR in EC and EPC to study the effect on cell survival, proliferation, adhesion, migration, and capillary-like tubes formation on matrigel, which all resulted impaired by p75NTR. We identified that p75NTR inhibits the VEGF-A/Akt/eNOS/NO pro-angiogenesis/pro-EC survival pathway and reduces the mRNA contents of survivin and securin in EC. By Illumina technology and real-time PCR, we found that p75-NTR alters the expression of VEGF-A and beta-1 integrin, which are implicated in angiogenesis and cell survival. p75NTR transfer to ischemic murine limb muscles impaired neoangiogenesis and blood flow recovery and induced apoptosis of bone marrow Sca-1+/Lin- progenitor cells. Diabetes induced p75NTR in bone marrow Sca-1+/Lin- cells and this correlated with apoptosis. Finally, inhibition of p75NTR signaling in diabetic ischemic limb muscles restored proper muscular neovascularization and blood flow recovery. Keywords: Response to ectopic receptor expression on angiogenesis Two series of 4 mice each were treated with either control adenovirus (AdNull) or adenovirus expressing neurotrophin p75 receptor (AdP75). Anaesthetized mice received 3 adenovirus injections (for a total of 109 p.f.u. virus in 20 micro L) into 3 equidistant sites of the normoperfused or ischemic left adductor muscles, as described (2. Emanueli C, Graiani G, Salis MB, Gadau S, Desortes E, Madeddu P. Prophylactic gene therapy with human tissue kallikrein ameliorates limb ischemia recovery in type 1 diabetic mice. Diabetes. 2004 Apr;53(4):1096-103. )
2010-06-25 | E-GEOD-9910 | biostudies-arrayexpress
Project description:The neurotrophin receptor p75NTR orchestrates chondrogenesis and mechano-adaptation to preserve temporomandibular joint growth and homeostasis (scRNA seq analysis)
| PRJNA1378910 | ENA
Project description:Neurotrophins (NTs) promotes angiogenesis and EC survival, via tropomyosin kinase trkA and trkB receptors. A different p75NTR receptor of NTs, which belongs to the TNF-alfa receptor superfamily, is not or scarcely expressed by endothelial cells (EC) and endothelial progenitor cells (EPC) under basal conditions. Both diabetes and muscular ischemia induce p75NTR in capillary EC. In this study, by gene transfer, we forced the expression of p75NTR in EC and EPC to study the effect on cell survival, proliferation, adhesion, migration, and capillary-like tubes formation on matrigel, which all resulted impaired by p75NTR. We identified that p75NTR inhibits the VEGF-A/Akt/eNOS/NO pro-angiogenesis/pro-EC survival pathway and reduces the mRNA contents of survivin and securin in EC. By Illumina technology and real-time PCR, we found that p75-NTR alters the expression of VEGF-A and beta-1 integrin, which are implicated in angiogenesis and cell survival. p75NTR transfer to ischemic murine limb muscles impaired neoangiogenesis and blood flow recovery and induced apoptosis of bone marrow Sca-1+/Lin- progenitor cells. Diabetes induced p75NTR in bone marrow Sca-1+/Lin- cells and this correlated with apoptosis. Finally, inhibition of p75NTR signaling in diabetic ischemic limb muscles restored proper muscular neovascularization and blood flow recovery. Keywords: Response to ectopic receptor expression on angiogenesis
2008-07-17 | GSE9910 | GEO
Project description:MicroRNAs (miRNAs) are small non-protein-coding RNAs that are incorporated into the RNA-induced silencing complex (RISC) and inhibit gene expression by regulating the stability and/or the translational efficiency of target mRNAs. p75NTR, which is scarcely present in healthy endothelial cells (ECs), becomes strongly expressed by capillary ECs after induction of peripheral ischemia in type-1 diabetic mice. p75NTR expression promotes endothelial cells apoptosis and inhibits angiogenesis. In order to identify miRNAs sub-sequentely modulated by p75NTR, miRNA expression profiles of human umbilical vein endothelial cells (HUVEC) over-expressing p75NTR were generated, allowing the identification of miRNAs modulated upon p75NTR up-regulation. HUVEC over-expressing p75NTR or Null (empty vector) were generated by adenoviral infection. miRNA expression profiles were then measured and miRNAs modulated upon p75NTR up-regulation were identified.
2014-01-11 | E-GEOD-53899 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small non-protein-coding RNAs that are incorporated into the RNA-induced silencing complex (RISC) and inhibit gene expression by regulating the stability and/or the translational efficiency of target mRNAs. p75NTR, which is scarcely present in healthy endothelial cells (ECs), becomes strongly expressed by capillary ECs after induction of peripheral ischemia in type-1 diabetic mice. p75NTR expression promotes endothelial cells apoptosis and inhibits angiogenesis. In order to identify miRNAs sub-sequentely modulated by p75NTR, miRNA expression profiles of human umbilical vein endothelial cells (HUVEC) over-expressing p75NTR were generated, allowing the identification of miRNAs modulated upon p75NTR up-regulation.
2014-01-11 | GSE53899 | GEO
Project description:The present study investigated the alterations of miRNA expression profiling in synovium of temporomandibular joint(TMJ) in a rat model of experimental unilateral mastication. The synovium tissue of TMJ condyles from rats with 4- and 8-weeks unilateral mastication were harvested to extract miRNA for profiling holistic expression alternations. A total of 20 differentially expressed miRNAs were identified. Except for 3 miRNAs with uncertain function, those miRNAs are associated with cell proliferation, invasion, and osteoblast differentiation process.
2018-05-16 | GSE114499 | GEO
Project description:Background Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. Materials and Methods To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. Results Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclast in the subchondal bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. Conclusions Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.
2024-03-19 | GSE261528 | GEO
Project description:We conducted a genetic analysis of the developing temporo-mandibular joint (TMJ), a highly specialized synovial joint that permits movement and function of the mammalian jaw. First, we used laser capture microdissection to perform a genome-wide expression analysis of each of its developing components. The expression patterns of genes identified in this screen were examined in the TMJ and compared to other synovial joints including the shoulder joint and the hip joint. Striking differences were noted, indicating that the TMJ forms via a distinct molecular program. Several components of the Hedgehog (Hh) signaling pathway are among the genes identified in the screen, including Gli2, which is expressed specifically in the condyle and in the disk of the developing TMJ. We found that mice deficient in Gli2 display aberrant TMJ development such that the condyle loses its growth plate-like cellular organization and no disk is formed. In addition, we utilized a conditional strategy to remove activity of the Hh co-receptor encoded by Smo from chondrocyte progenitors. This cell autonomous loss of Hh signaling allows for disk formation, but the resulting structure fails to separate from the condyle. Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation and disk-condyle separation, and provide a molecular framework for future studies of the TMJ. Experiment Overall Design: Mouse embryos fresh frozen and TMJ tissue captured by LCM. 3 samples in biological triplicate.
2009-10-23 | E-GEOD-17473 | biostudies-arrayexpress
Project description:Comparison of gene expression patterns in liver of wildtype and p75NTR knockout mice
2019-05-01 | GSE122424 | GEO
Project description:Background: Temporomandibular joint (TMJ) degenerative diseases are increasingly affecting elderly populations, with aging being a significant risk factor driving the TMJ changes. This study aims to explore the shared characteristics between aging and TMJ degenerative diseases at the tissue level, and to identify aging-related signature genes in TMJ degenerations using bioinformatics approaches. Methods: Young (2 months of age, n=7) and aged (18 months of age, n=6) mice’s condyles were used to construct an aging dataset. Overlapping genes were selected from differentially expressed genes in the TMJOA dataset, aging dataset and mechanical stimulation dataset. Temporomandibular joint osteoarthritis-associated and aging-related differentially expressed genes (TMJOA-ARDEGs) were identified through Weighted gene co-expression network analysis. Functional enrichment analysis and Protein-Protein Interaction networks were employed. Machine learning was applied to select Hub temporomandibular joint osteoarthritis-associated and aging-related differentially expressed genes (Hub TMJOA-ARDEGs). An age-related TMJOA mouse model (18 months of age) was established and grouped based on the micro-CT and the modified Mankin scores. The expression changes of key Hub TMJOA-ARDEGs were verified by immunohistochemical staining. The Mann-Whitney U test was used in non-normally distributed data, presented as [median (interquartile range)]. Results: Fifty-two TMJOA-ARDEGs were identified, with functional enrichment analysis revealed that these genes participate in circadian rhythm and apoptosis. Eight Hub TMJOA-ARDEGs were identified, ANK1, MELTF, FERMT3, MDFI, CXCL14, EPHA3, SMOC2 and NR1D1. Based on the micro-CT, 12 TMJs of aged mice were divided into the TMJOA group (n=6) and the healthy group (n=6). Micro-CT revealed bone resorption in the TMJOA group compared to the healthy group, with a decrease in BV/TV (p<0.05) and an increase in Tb.Sp (p<0.05). The modified Mankin scores showed that the TMJOA group had a score of 5.61 (2.28), higher than the healthy group's score of 0.83 (1.28), p<0.01. These results confirm the validity of the model grouping. Among the Hub TMJOA-ARDEGs, NR1D1 is a key gene involved in regulating circadian rhythm. In immunohistochemical staining, the expression level of NR1D1 showed significantly elevated expression in osteoarthritis mice (p<0.01). Conclusion: NR1D1, a negative feedback regulator in the circadian rhythm loop, is a characteristic gene associated with both aging and TMJ degenerative diseases.
2026-04-26 | GSE315467 | GEO