Macrophage-derived ectosomal miR-350-3p promotes osteoarthritis progression through downregulating chondrocyte H3K36 methyltransferase NSD1

Quick Facts

  • Publication title: Macrophage-derived ectosomal miR-350-3p promotes osteoarthritis progression through downregulating chondrocyte H3K36 methyltransferase NSD1
  • Journal: Cell Death Discov
  • Year: 2024
  • DOI: 10.1038/s41420-024-01986-5
  • PMID/PMCID: 38719811; PMC11078928

Research overview

Here, we found that macrophages exhibited M1 polarization under mechanical overloading and secreted ectosomes that induced cartilage degradation and senescence. This study demonstrated that the targeting of macrophage-derived ectosomal miRNAs was a potential therapeutic method for mechanical overload-induced OA.

Key findings

Mechanical overloading can promote cartilage senescence and osteoarthritis (OA) development, but its impact on synovial macrophages and the interaction between macrophages and chondrocytes remain unknown.

Here, we found that macrophages exhibited M1 polarization under mechanical overloading and secreted ectosomes that induced cartilage degradation and senescence.

By performing miRNA sequencing on ectosomes, we identified highly expressed miR-350-3p as a key factor mediating the homeostatic imbalance of chondrocytes caused by M1-polarized macrophages, this result being confirmed by altering the miR-350-3p level in chondrocytes with mimics and inhibitor.

In experimental OA mice, miR-350-3p was increased in synovium and cartilage, while intra-articular injection of antagomir-350-3p inhibited the increase of miR-350-3p and alleviated cartilage degeneration and senescence.

Echo Biotech Role

Echo Biotech contributed EV isolation and purification, EV characterization, miRNA profiling/sequencing and bioinformatic analysis.

Related platforms: Exoomics®

Related services and capabilities: EV Isolation & Purification, EV Basic Characterization (TEM/NTA/WB), EV miRNA Profiling / Sequencing

References

Original publication: Macrophage-derived ectosomal miR-350-3p promotes osteoarthritis progression through downregulating chondrocyte H3K36 methyltransferase NSD1 Cell Death Discov. 2024. DOI: 10.1038/s41420-024-01986-5. PMID/PMCID: 38719811; PMC11078928.