NG2/CSPG4 regulates cartilage degeneration during TMJ osteoarthritis
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PROVIDER: PRJNA883722 | ENA |
REPOSITORIES: ENA
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Project description:Changes in the mechanical homeostasis of the temporomandibular joint (TMJ) can lead to the initiation and progression of degenerative arthropathies such as osteoarthritis (OA). Cells sense and engage with their mechanical microenvironment through interactions with the extracellular matrix. In the mandibular condylar cartilage, the pericellular microenvironment is composed of type VI collagen. NG2/CSPG4 is a transmembrane proteoglycan that binds with type VI collagen, and has been implicated in the cell stress response through mechanical loading-sensitive signaling networks including ERK 1/2. The objective of this study is to define the role of NG2/CSPG4 in the initiation and progression of TMJ OA and to determine if NG2/CSPG4 engages ERK 1/2 in a mechanical loading dependent manner. In vivo, we induced TMJ OA in control and NG2/CSPG4 knockout mice using a surgical destabilization approach. In control mice, NG2/CSPG4 is depleted during the early stages of TMJ OA and NG2/CSPG4 knockout mice have more severe cartilage degeneration, elevated expression of key OA proteases, and suppression of OA matrix synthesis genes. In vitro, we characterized the transcriptome and protein from control and NG2/CSPG4 knockout cells and found significant dysregulation of the ERK 1/2 signaling axis. To characterize the mechanobiological response of NG2/CSPG4, we applied mechanical loads on cell-agarose-collagen scaffolds using a compression bioreactor and illustrate that NG2/CSPG4 knockout cells fail to mechanically activate ERK 1/2 and are associated with changes in the expression of the same key OA biomarkers measured in vivo. Together, these findings implicate NG2/CSPG4 in the mechanical homeostasis of TMJ cartilage and in the progression of degenerative arthropathies including OA.
2022-09-24 | GSE214077 | GEO
Project description:Changes in the mechanical homeostasis of the temporomandibular joint (TMJ) can lead to the initiation and progression of degenerative arthropathies such as osteoarthritis (OA). Cells sense and engage with their mechanical microenvironment through interactions with the extracellular matrix. In the mandibular condylar cartilage, the pericellular microenvironment is composed of type VI collagen. NG2/CSPG4 is a transmembrane proteoglycan that binds with type VI collagen, and has been implicated in the cell stress response. The objective of this study is to define the role of NG2/CSPG4 in the cell stress response during serum starvation. To evaluate the role of the NG2/CSPG4, primary mandibular fibrochondrocytes from c57 BL/6 J and NG2/CSPG4 knockout mice (mixed sex) were cultured in normal and serum starvation conditions. To evaluate the role of the NG2/CSPG4 ectodomain, primary mandibular fibrochondrocytes were immortalized using hTERT. CRSIPR/Cas9 was used to truncate the NG2/CSPG4 ectodomain by targeting the type VI collagen binding region. Normal culture conditions were AMEM growth media supplemented with 10% FBS, penicillin, L-Glut, and plasmocin. Serum starvation conditions were Optimem media with no FBS, supplemented with penicillin, L-Glut, and plasmocin. Serum starvation was induced for 24 hours. RNA from the cells was isolated using the RNeasy kit (Qiagen). poly(A) RNA was fragmented using divalent cation buffer in elevated temperature. The DNA library construction is shown in the following workflow. Quality control analysis and quantification of the sequencing library were performed using Agilent Technologies 2100 Bioanalyzer High Sensitivity DNA Chip. Paired-ended sequencing was performed on Illumina’s NovaSeq 6000 sequencing system. Sequencing was done by LC Sciences. These data illustrate that in serum starvation conditions, NG2/CSPG4 knockout mandibular fibrochondrocytes and targeted truncation of the NG2/CSPG4 ectodomain alters the transcriptional profile of the cell, promoting biological processes associated with cell stress, migration, and ossiciation.
2024-10-30 | GSE245590 | GEO
Project description:Changes in the mechanical homeostasis of the temporomandibular joint (TMJ) can lead to the initiation and progression of degenerative arthropathies such as osteoarthritis (OA). Cells sense and engage with their mechanical microenvironment through interactions with the extracellular matrix. In the mandibular condylar cartilage, the pericellular microenvironment is composed of type VI collagen. NG2/CSPG4 is a transmembrane proteoglycan that binds with type VI collagen, and has been implicated in the cell stress response. The objective of this study is to define the role of NG2/CSPG4 in the cell stress response during serum starvation. To evaluate the role of the NG2/CSPG4, primary mandibular fibrochondrocytes from c57 BL/6 J and NG2/CSPG4 knockout mice (mixed sex) were cultured in normal and serum starvation conditions. To evaluate the role of the NG2/CSPG4 ectodomain, primary mandibular fibrochondrocytes were immortalized using hTERT. CRSIPR/Cas9 was used to truncate the NG2/CSPG4 ectodomain by targeting the type VI collagen binding region. Normal culture conditions were AMEM growth media supplemented with 10% FBS, penicillin, L-Glut, and plasmocin. Serum starvation conditions were Optimem media with no FBS, supplemented with penicillin, L-Glut, and plasmocin. Serum starvation was induced for 24 hours. RNA from the cells was isolated using the RNeasy kit (Qiagen). poly(A) RNA was fragmented using divalent cation buffer in elevated temperature. The DNA library construction is shown in the following workflow. Quality control analysis and quantification of the sequencing library were performed using Agilent Technologies 2100 Bioanalyzer High Sensitivity DNA Chip. Paired-ended sequencing was performed on Illumina’s NovaSeq 6000 sequencing system. Sequencing was done by LC Sciences. These data illustrate that in serum starvation conditions, NG2/CSPG4 knockout mandibular fibrochondrocytes and targeted truncation of the NG2/CSPG4 ectodomain alters the transcriptional profile of the cell, promoting biological processes associated with cell stress, migration, and ossiciation.
2023-11-30 | GSE245589 | GEO
Project description:NG2/CSPG4 is expressed in soft tissue sarcomas, however, its function in this tumor type, and its capacity to serve as a therapeutic target are unknown. Here, we used genetically engineered mice and cells from human tumors to determine the function of Ng2/Cspg4 in soft tissue sarcoma initiation and growth. We also investigated the potential for NG2/CSPG4 mAb immunotherapy to target human sarcomas established as xenografts in mice. Inhibiting Ng2/Cspg4 expression in established soft tissue sarcomas is associated with a smaller tumor volume and a reduction in cell proliferation. Intriguingly, deleting Ng2/Cspg4 at the time of tumor initiation has the opposite effect. Gene profiling found that Igfbp3/5 are substantially downregulated when Ng2/Cspg4 is depleted at the time of tumor initiation, but upregulated or only minimally downregulated when Ng2/Cspg4 is depleted after tumor initiation. Furthermore, the normal regulation of Igfbp is blunted when Ng2/Cspg4 is deleted at the time of tumor initiation. Our data show a difference in NG2/CSPG4 function in tumor initiation and maintenance, and provides pre-clinical evidence supporting NG2/CSPG4 as a therapeutic approach in soft tissue sarcoma.
2017-04-07 | GSE97489 | GEO
Project description:HPIP controls osteoarthritis cartilage degeneration
| PRJNA391300 | ENA
Project description:Temporomandibular joint osteoarthritis (TMJ-OA), a subtype of temporomandibular joint dysfunction (TMD), is characterized by progressive cartilage degradation, subchondral bone erosion, and chronic pain. Although there has been extensive research on TMJ-OA, its etiology remains unknown. Age, hormonal factors, and excessive mechanical stress on the TMJ are proposed risk factors for TMJ-OA. Using microarrays, we discovered two disease susceptibility genes that have been suggested to be involved in the pathogenic mechanism of TMJ-OA.
2020-09-18 | GSE158106 | GEO
Project description:Osteoarthritis (OA) is the most prevalent joint disease with the typifying feature being the progressive degradation of articular cartilage during disease progression. In this study we used whole transcriptome RNA-seq as a tool to compare gene expression changes between age-matched osteoarthritic human hip OA cartilage (n=10) compared to control (neck of femur fracture) cartilage (n=6) [GSE107308]. All cartilage was from patients undergoing acetabulofemoral joint replacement. Cartilage RNA was isolated from cartilage within 2 hr of joint replacement surgery, mRNA was polyA purified and transcript expression was analysed using 78-base paired-end sequencing generating on average 28 million reads/sample sequencing. The data shows excellent correlation with our previous microarray data but identifies significantly more differentially expressed transcripts plus novel transcript variants, several of which have been validated by real-time qPCR. Our work sheds further light on chondrocyte transcriptome expression and highlights gene expression changes and novel transcripts potentially important in osteoarthritis progression
2019-03-01 | GSE111357 | GEO
Project description:NG2/CSPG4 regulates the transcriptional profile of mandibular fibrochondrocytes during serum starvation
| PRJNA1029036 | ENA
Project description:Articular cartilage is deprived of blood vessels and nerves, and the only cells residing in this tissue are chondrocytes. The molecular properties of the articular cartilage and the architecture of the extracellular matrix demonstrate a complex structure that differentiates on the depth of tissue. Osteoarthritis (OA) is a degenerative joint disease, the most common form of arthritis, affecting the whole joint. It is associated with ageing and affects the joints that have been continually stressed throughout life including the knees, hips, fingers, and lower spine region. OA is a multifactorial condition of joint characterised by articular cartilage loss, subchondral bone sclerosis, and inflammation leading to progressive joint degradation, structural alterations, loss of mobility and pain. Articular cartilage biology is well studied with a focus on musculoskeletal diseases and cartilage development. However, there are relatively few studies focusing on zonal changes in the cartilage during osteoarthritis.
2022-05-19 | PXD029116 | Pride
Project description:Osteoarthritis (OA) of spine (facet joints; FJ) is one of the major causes of severe low back pain and disability worldwide. The degeneration of facet cartilage is a hallmark of FJ OA. However, endogenous mechanisms that initiate degeneration of facet cartilage are unknown and there are no disease-modifying therapies to stop FJ OA. In this study we performed microRNA array analysis to identify differentially expressed microRNAs in facet cartilage from patients with FJ OA compared to facet cartilage from patients with lumbar disc herniation (LDH).
2016-03-15 | GSE79258 | GEO