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Unveiling the Mechanisms of Mechanical Loading-Induced Knee Osteoarthritis Through Transcriptomics

ABSTRACT: Unveiling the Mechanisms of Mechanical Loading-Induced Knee Osteoarthritis Through Transcriptomics

PROVIDER: PRJNA1156783 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR30559762_1.fastq.gz	Fastqsanger.gz
	SRR30559762_2.fastq.gz	Fastqsanger.gz
	SRR30559763_1.fastq.gz	Fastqsanger.gz
	SRR30559763_2.fastq.gz	Fastqsanger.gz
	SRR30559764_1.fastq.gz	Fastqsanger.gz

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Unveiling the Mechanisms of Mechanical Loading-Induced Knee Osteoarthritis Through Transcriptomics

Project description:Aims：To establish a novel model of mechanical loading-induced knee osteoarthritis (KOA) and explore its regulatory mechanisms through transcriptomics. Methods：Knee joints of Sprague-Dawley (SD) rats were mechanically loaded with 13 N, 20 N and 27 N for 2 or 4 weeks to construct mechanically-induced KOA model. Immunohistochemistry (IHC), quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, Safranin O/fast green staining, enzyme-linked immunosorbent assay (ELISA), micro-computed tomography (Micro-CT) and behavioral analysis were used to evaluate damage on the right knee joint. Transcriptomic analysis combined with validation experiments were performed to explore the regulatory mechanism of excessive mechanical loading on KOA development. Results：A vertical load of 27 N resulted in calf fractures, whereas a 13 N load did not cause remarkable pathological alteration in the knee joint. Notably, applying compression at a load of 20 N for 4 weeks (w) significantly promoted the levels of pro-inflammatory factors IL-6, IL-β and TNF-α in serum and joint fluids and markedly minimized the levels of anti-inflammatory factors IL-10 and TGF-β. Immunohistochemistry, qRT-PCR and Western blot analyses suggested that the 20 N load reduced the expression of anabolism markers (ACAN and COL2A1) and escalated the expression of catabolism markers (MMP13 and ADAMTS4). KEGG analysis and validation results showed that the PIEZ1 channel, Ca2+ signaling pathway, PI3K-AKT signaling pathway and NF-κB signaling pathway were significantly activated in the 20N-4 w group. Conclusion：Continuous loading with 20 N for 4 weeks can induce significant OA-like damage to the cartilage of the right knee in rats, which might be induced through the piezo1-Ca2+/PI3K-AKT/ NF-κB signaling pathway.

2024-09-05 | GSE276365 | GEO

Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading

Project description:Evidences indicate that mechanical loading plays an important role in osteoarthritis (OA) progression, while the specific pathological changes of the synovium under excessive mechanical loading are unclear. Results showed excessive mechanical loading caused pro-inflammatory of synovial macrophages, which has been confirmed to exists in OA. High Rapgef3 expression level was found in RNA sequencing of RAW246.7 subjected to 0.5Hz-20%-cyclic tensile strain. We verified this in the synovium of OA patients and DMM-OA mice. Interestingly, the Rapgef3 content of chondrocytes was very low. Primary chondrocytes treated with Rapgef3 alone did not show metabolic phenotype, but an OA phenotype appeared when treated with Rapgef3-stimulated macrophage culture supernatant. Mechanically, excessive mechanical loading activated p65-NF-κB pathway through Rapgef3, which promoted the inflammatory of macrophage, resulting in severe articular cartilage injury. Intra-articular Rapgef3 knockout reversed synovitis and cartilage degeneration, which might provide a therapeutic target for osteoarthritis.

2024-11-04 | GSE280230 | GEO

Synovial Macrophage Activation Profiles in Experimental Knee Osteoarthritis

Project description:To investigate differences in gene expression of synovial macrophages in experimental rat knee post traumatic osteoarthritis.

2024-03-22 | GSE216932 | GEO

Mechanical loading and gene expression - Microarray study

Project description:Skeletal integrity in humans and animals is maintained by daily mechanical loading. It has been widely accepted that osteocytes function as mechanosensors. Many biochemical signaling molecules are involved in the response of osteocytes to mechanical stimulation. The aim of this study was to identify genes involved in the translation of mechanical stimuli into bone formation. The four-point bending model was used to induce a single period of mechanical loading (comprising 300 cycles (2 Hz) using a peak magnitude of 60 N) on the right tibia, while the contra lateral left tibia served as control. Six hours after loading, the effects of mechanical loading on gene-expression were determined with microarray analysis. Protein expression of differentially regulated genes was evaluated with immunohistochemistry. Nine genes were found to exhibit a significant differential gene expression in LOAD compared to control. MEPE, Garnl1, V2R2B, and QFG TN1 olfactory receptor were up-regulated, and creatine kinase (muscle form), fibrinogen-B beta-polypeptide, monoamine oxidase A, troponin-C and kinesin light chain-C were down-regulated. Validation with real-time RT-PCR analysis confirmed the up regulation of MEPE and the down-regulation of creatine kinase (muscle form) and troponin-C in the loaded tibia. Immunohistochemistry showed that the increase of MEPE protein expression was already detectable six hours after mechanical loading. In conclusion, these genes probably play a role during translation of mechanical stimuli six hours after mechanical loading. The modulation of MEPE expression may indicate a connection between bone mineralization and bone formation after mechanical stimulation. Two groups: LOAD vs contralateral control and SHAM vs contralateral control (n=5/group)

2013-11-21 | E-GEOD-50707 | biostudies-arrayexpress

Bulk RNA-seq of human knee osteoarthritis synovium

Project description:To classify knee osteoarthritis (OA) synoviums according to gene expression patterns, we performed RNA-seq using synovial tissues obtained from OA patients and non-OA patients.

2025-01-07 | GSE283079 | GEO

Transcriptome sequencing of synovial tissues of knee osteoarthritis rats.

Project description:Using transcriptome sequencing to screen the differntent expression genes in MIA-induced knee osteoarthritis (KOA) model rats compared with normal rats.

2024-06-22 | GSE206678 | GEO

Single cell RNA-seq of human knee osteoarthritis synovium

Project description:To classify knee osteoarthritis (OA) synoviums according to gene expression patterns, we performed single cell RNA-seq using synovial tissues obtained from OA patients.

2025-01-07 | GSE283080 | GEO

Regulatory constraint and selection during human knee evolution drive modern osteoarthritis risk

Project description:The evolution of human bipedalism exposed the knee to unique biomechanical challenges, requiring changes in knee anatomy giving rise to the modern-day configuration. In order to better understand the relationship between derived knee morphology and the genetic factors associated with osteoarthritis risk, we performed epigenetic profiling of murine forelimb/hindlimb growth plates to identify regulatory elements shaping formation of specific knee structures, identifying signals of ancient positive selection upon which more recent genetic drift overlaps risk-associated loci. Our functional analyses of an osteoarthritis-risk variant within a reproducibly-associated locus establishes a novel model for studying this degenerative disease.

2020-04-16 | GSE122877 | GEO

Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading

Project description:Rapgef3 modulates macrophage reprogramming and exacerbates synovitis and osteoarthritis under excessive mechanical loading

| PRJNA1177415 | ENA

Sequencing of the effect of mechanical stimulation on mesenchymal stem cells

Project description:Mechanical force is a crucial external stimulus that plays a significant role in regulating bone structure and remodeling. Excessive loading of the bone and joint can lead to increased catabolism, chondrocyte necrosis, apoptosis and damage to the collagen network of bone(3–5). Osteoarthritis (OA), a degenerative osteoarticular disease, is associated with abnormal mechanical force stimulation, which can occur in various joints such as knee, temporomandibular joint [TMJ], shoulder and hip(6). Conversely, the absence of mechanical loading, such as prolonged bed rest or exposure to a microgravity environment in space, can result in a rapid decrease in bone mass and strength. Understanding how mechanical stimuli regulate bone homeostasis is crucial for exploring therapeutic strategies for bone metabolic diseases.Mesechymal stem cells (MSCs) act as the external force sensoring and compression-bearing elements.What we want to explore is how mechanical stimulation affects the genome changes of mesenchymal stem cells.

2023-11-13 | GSE247273 | GEO

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