Genetically inspired organoids prevent joint degeneration and alleviate chondrocyte senescence via Col11a1–HIF1α‐mediated glycolysis–OXPHOS metabolism shift

Abstract

We reported association between COL11A1 loci and DDH with GWAS and exome sequencing. Further studies demonstrated involvement of COL11A1 in DDH patients and Col11a1-KO mice. ScRNA-seq for DDH and Col11a1-KO cartilage demonstrated disrupted chondrocyte homeostasis and cellular senescence caused by Col11a1-HIF1α-mediated glycolysis-OXPHOS shift in chondrocytes. Genetically and biologically inspired, an intra-articular injection therapy was fabricated to prevent cartilage degeneration with Col11a1-OE SMSC organoids. Col11a1-OE organoids ameliorated cartilage degeneration in DDH mice via regulating cellular senescence by up-regulated Col11a1/HIF1α-mediated glycolysis in chondrocytes.