Dataset Information

Rat knee joint scRNA-seq data with meniscus injury treated by 4PPBP

ABSTRACT: Avascular meniscus tears are a major contributor to mechanical joint locking, compromised gait and function, and the initiation and progression of post-traumatic osteoarthritis. Unfortunately, the avascular meniscus tears hardly heal. Here, we report a novel small molecule, 4-PPBP, a sigma-1 receptor (σ1R) agonist, exhibiting significant potential to promote avascular meniscus healing by activating synovial mesenchymal stem cells (syMSCs) and modulating macrophage-regulated inflammation via multi-tissue crosstalk. In vivo, a single injection of 4-PPBP-loaded bioglue minimized meniscal gapping, with improved meniscus healing and gait performance. In contrast to the degenerative changes in the untreated control, 4-PPBP/bioglue application resulted in integrated fibrocartilaginous tissues. scRNA-seq and CellChat analyses revealed 4-PPBP-activated cell-cell communications leading to inflammatory regulation and cell differentiation. Macrophages showed a robust reduction in pro-inflammatory genes, and fibroblasts, chondrocytes, and fibrochondrocytes increased genes associated with differentiation and matrix synthesis in response to 4-PPBP. Anti-inflammatory cell-cell communication signals were significantly elevated between adipocytes and macrophages.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE317855 | GEO | 2026/04/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: Meniscus tears are the most common injury in the knee and are associated with an increased risk of osteoarthritis (OA). The molecular profile of knees with meniscus tears is not well-studied. Therefore, to advance our understanding of the early response of the knee to injury, we compared the gene expression profile of meniscus and articular cartilage within the same knees following meniscus injury. Hypothesis/Purpose: To identify differences between the molecular signatures of meniscus and articular cartilage from knees with intact articular cartilage undergoing arthroscopic partial meniscectomy. Study Design: Descriptive laboratory study Methods: Patients (n=12) with a known isolated medial meniscus tear without any knee chondrosis or radiographic OA were consented prior to surgery. During arthroscopic partial meniscectomy, a sample of their injured meniscus and a sample of their articular cartilage off the medial femoral condyle were procured. The transcriptome signatures, as measured through Affymetrix microarray, were compared between the two tissues and underlying biological processes were explored computationally. Results: 3566 gene transcripts were differentially expressed between meniscus and articular cartilage. Gene transcripts down-regulated in articular cartilage were associated with extracellular matrix organization, wound healing, cell adhesion, and chemotaxis. Gene transcripts up-regulated in articular cartilage were associated with blood vessels morphogenesis and angiogenesis. Examples of individual genes with significant differences in expression between the two tissues include IBSP (23.76 fold; P < 0.001), upregulated in meniscus, and TREM1 (3.23 fold; P = 0.006), upregulated in meniscus. Conclusion: The meniscus and articular cartilage have distinct gene expression profiles in knees with meniscus tears and intact articular cartilage. Total RNA obtained from injured meniscus and normal articular cartilage from patients undergoing partial meniscectomy.

Project description:The anterior cruciate ligament (ACL) is an essential stabilizer of the tibiofemoral articulation. ACL tears often lead to functional instability and are associated with an increased risk for osteoarthritis. The healing potential of the injured ACL is poorly understood and is considered to be limited. Transcriptome-wide expression profiles of 24 human ACL remnants recovered at the time of surgical reconstruction were analyzed utilizing the Agilent human 8x60K microarray platform. Gene ontology was performed on differentially expressed transcripts based on time-from-injury (acute, <3 months; intermediate, 3-12 months; chronic, >12 months). A subset of transcripts was validated via microfluidic digital polymerase-chain-reaction. Expression of periostin, a highly differentially expressed transcript, was tested by immunohistochemistry. Numerous transcripts covering important functional classifications were differentially expressed by time-from-injury. In acute tears, processes representing angiogenesis were repressed while those representing stem-cell differentiation were elevated. In intermediate tears, processes representing stem-cell proliferation concomitant with cellular component organization/cellular localization were elevated. In chronic tears, processes denoting myosin filament organization were elevated while those representing cellular component organization/cell localization and extracellular matrix organization were repressed. Expression levels of periostin were down-regulated in chronic tears compared to acute (42-fold) and intermediate (29-fold) tears. Immunohistochemistry confirmed a decline in periostin expression in tissues from chronic tears. These findings suggest an initial attempt of the injured ACL to repair, which declines with time-from-injury. These findings have implications for efforts to repair the ACL and may be relevant for reconstruction of the ACL. The functional role of periostin in ACL injuries, and the potential implication for surgical treatment, warrants further investigation. Total RNA obtained frominjured anterior cruciate ligament (ACL) tissues from pateints undergoing ACL surgery.

Dataset Information

Rat knee joint scRNA-seq data with meniscus injury treated by 4PPBP

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets