Abstract
Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage and/or chondrocyte destruction, and although it has long been considered as a primary disease, the importance of meniscus endothelial cell modulation in the subchondral microenvironment has recently drawn attention. Previous studies have shown that apelin could potentially inhibit cellular apoptosis; however, it remains unclear whether apelin could play a protective role in protecting the endothelium in the OA meniscus. In this study, with the advantages of single-cell RNA sequencing (scRNA-seq) data, in combination with flow cytometry, we identified two endothelial subclusters in the meniscus, featured by high expression of Homeobox A13 (HOXA13) and Ras Protein-Specific Guanine Nucleotide Releasing Factor 2 (RASGRF2), respectively. Compared with control patients, both subclusters decreased in absolute cell numbers and exhibited downregulated APJ endogenous ligand (APLN, coding for apelin) and upregulated apelin receptor (APLNR, coding apelin receptor). Furthermore, we confirmed that in OA, decreased endothelial cell numbers, including both subclusters, were related to intrinsic apoptosis factors: one more relevant to caspase 3 (CASP3) and the other to BH3-Interacting Domain Death agonist (BID). In vitro culturing of meniscal endothelial cells purified from patients proved that apelin could significantly inhibit apoptosis by downregulating these two factors in endothelial cell subclusters, suggesting that apelin could potentially serve as a therapeutic target for patients with OA.
Highlights
Osteoarthritis (OA), a degenerative joint disease, is generally associated with obesity and ageing
This study reported that apelin alleviates meniscal endothelial cell apoptosis in patients with OA by inhibiting caspase 3 (CASP3) and BH3-Interacting Domain Death agonist (BID) in different EC clusters
Existing studies indicate that tissue-specific endothelial cells exhibit distinguished subclusters, genetic profiles, and biomarkers among diseases
Summary
Osteoarthritis (OA), a degenerative joint disease, is generally associated with obesity and ageing. The vasculature in the joint was observed to be abnormal in patients with OA [1, 5], its molecular mechanism is still difficult to understand, as research is impacted by a technique limitation in acquiring sufficient endothelial cells. The rise of the scRNA-seq technique allows for exploring transcriptome in a highthroughput manner at a single-cell level so that the endothelial cell heterogeneity can be studied more conveniently [6, 7]. Endothelial cells in different organs (e.g., brain, lung, and heart) exhibit tissue-specific heterogeneity, characterized by molecular signatures such as those related to pathways and cell-surface markers [6–8]. Research on tissue-specific endothelial cell heterogeneity will help to understand the development of various diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
