Apelin Alleviates Meniscus Endothelial Cell Apoptosis in Osteoarthritis

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.

Single‐cell RNA sequencing in osteoarthritis

“…Vascularization of this region is the most active while the other two zones are avascular to a different degree 105 . According to such heterogeneity in vascularity, scRNA‐seq discovered that endothelial cells played an important role in meniscus degeneration 106 . ECs (endothelial cells in meniscus) progenitors (marked with CD146+) can not only generate vessels to maintain a blood supply, but also promote the migration of meniscus cells.…”

“…Prevent ECM degradation and promote reparative anabolic processes [72] Cartilage tissue from 10 OA patients CPCs Repair cartilage [53] HTC Human articular cartilage samples GPX4 Anti-ferroptotic effect of Trpv1 in OA cartilage [76] Human meniscus samples FCP Progenitors in OA meniscus [100] ALPN Antiapoptotic maintaining vascular activity in the red-zone of meniscus [106] Human subchondral bone samples Pre-ECs and EC Pathological angiogenesis coupling with aberrant osteogenesis to accelerate OA progression in the subchondral bone [113] Synovial joint tissue ACKR4 Decrease chondrocyte catabolism [85] Human F I G U R E 8 scRNA-seq links potential clinical applications with pre-clinical studies on OA. Singlecell RNA sequencing is a promising technology in preclinical studies to identify potential molecular mechanisms or targets in OA and will be applied as a fundamental method in all aspects of OA clinical studies in the future.…”

“… 105 According to such heterogeneity in vascularity, scRNA‐seq discovered that endothelial cells played an important role in meniscus degeneration. 106 ECs (endothelial cells in meniscus) progenitors (marked with CD146+) can not only generate vessels to maintain a blood supply, but also promote the migration of meniscus cells. (Figure 5A ) Two ECs subclusters in OA patients were respectively marked with HOXA13 and RASGRF2.…”

Retracted: Apelin Alleviates Meniscus Endothelial Cell Apoptosis in Osteoarthritis

“…

This article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:

…”

“…This article has been retracted by Hindawi following an investigation undertaken by the publisher [ 1 ]. This investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process: Discrepancies in scope Discrepancies in the description of the research reported Discrepancies between the availability of data and the research described Inappropriate citations Incoherent, meaningless and/or irrelevant content included in the article Peer-review manipulation …”