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Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis [Spatial Transcriptomics]

ABSTRACT: Objective: To spatially resolve the identified celltypes, subtypes and transcriptomic profiles from single-nuclei RNA-seq with matched 12 infrapatellar fat pad of knee OA patients using spatial transcriptomics sequencing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE253199 | GEO | 2024/10/07

REPOSITORIES: GEO

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Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis [snRNA-seq]

Project description:Objective: To identify and characterize celltypes and distinct transcriptomic signatures present in the infrapatellar fat pad (IFP) of knee OA patients using single-nucleus RNA sequencing.

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Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis

Project description:Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis

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Project description:Infrapatellar fat pad (IPFP) and synovium, two joint tissues next to each other, play essential roles in regulating joint homeostasis and the progression of knee osteoarthritis (OA). However, the mechanisms regulating their function under healthy and diseased conditions are largely unknown. This study aims to analyze the cellular heterogeneity of these two tissues from normal and OA patients. Single cell and single nuclei transcriptomic profiling were performed on IPFP/synovium cells from four healthy donors and five OA patients. Subsequent bioinformatic analyses identified cell clusters, delineated differentiation routes of mesenchymal cells and macrophages, and identified novel cell-to-cell communication pathways in joint tissue.

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Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis [snRNA-seq]

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Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis [Spatial Transcriptomics]

Project description:Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis [Spatial Transcriptomics]

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Synovium and Infrapatellar fat pad are one functional tissue unit sharing common mesenchymal progenitors and undergoing coordinated changes in osteoarthritis

Project description:The Infrapatellar fat pads (IFP) are two wedge shaped fatty structures situated below the kneecap (patella), lying either side of the patellar tendon, first described by Hoffa in 1904. Recent studies reveal that knee OA causes pathological fibrosis, stiffening, and inflammation of the synovium and IFP (4, 5) (6). Multiple groups, including our co-investigator Dr. Changhai Ding, reported that MRI signal intensity alteration in IFP is strongly associated with OA knee structural abnormalities and may serve as an imaging biomarker to predict OA progression in patients (7-10). However, we have limited knowledge regarding the regulation of synovium and IFP functions for joint homeostasis and OA development.

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Proteomic Analysis of Infrapatellar Fat Pad in Osteoarthritis

Project description:The infrapatellar fat pad (IFP) is involved in the occurrence and progression of osteoarthritis (OA), yet the proteomic changes in the IFP during OA are not well understood. In this study, we selected the IFP from patients undergoing late-stage total knee arthroplasty as the experimental group, while the IFP from patients undergoing repair surgery for acute anterior cruciate ligament rupture served as the control group. Using label-free protein quantification technology, we analyzed the protein expression levels in the experimental and control groups. We identified 315 differentially expressed proteins that are primarily associated with functions such as coagulation, complement, fatty acid metabolism, and adipogenesis. These findings shed light on the potential molecular mechanisms underlying the involvement of the IFP in OA pathogenesis.

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Cell and Transcriptomic Diversity of Infrapatellar Fat Pad during Knee Osteoarthritis

Project description:This SuperSeries is composed of the SubSeries listed below.

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Osteoarthritis-related changes in gene expression in knee articular chondrocytes in a rat model of osteoarthritis.

Project description:Cartilage destruction in osteoarthritis (OA) results from disturbed chondrocyte metabolism. Here, we used microarrays to show that TGF alpha and CCL2 are simultaneously upregulated in a rat model of OA and cooperate to drive cartilage degradation. The goals of the experiments included here were to a) characterize gene expression in knee joint articular chondrocytes at various stages of development of OA (2 and 8 weeks after surgical induction of OA), and b) to establish trends in gene expression among groups of genes related to the TGF alpha-EGFR axis, over time, in OA. The model chosen to study these results has been previously validated (Appleton, CT et al, 2007, Arthritis Rheum) and used to describe similar gene expression results at a different time point (4 weeks) after induction of OA. The rat model of OA involves surgical destabilization of the knee joint, followed by forced low-intensity mobilization over several weeks; a sham surgery is used as the control (representing a healthy non-OA knee joint) wherein a surgical incision is made but not structural (i.e. ligamentous) modification is made to the joint. Altogether, our data indicate that TGF and CCL2 cooperate to drive cartilage degradation in osteoarthritis. A total of 12 samples were analyzed. 3 replicates were used per condition: OA surgery at 2 weeks, OA surgery at 8 weeks, Sham (control) surgery at 2 weeks and Sham surgery at 8 weeks. Expression of OA samples was assessed relaitve to Sham (control) expression levels.

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