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Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis

Author

Listed:
  • Jia Q. Ng

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Toghrul H. Jafarov

    (Columbia University Medical Center)

  • Christopher B. Little

    (Raymond Purves Bone & Joint Research Laboratories, Kolling Institute, University of Sydney Faculty of Medicine and Health, Royal North Shore Hospital)

  • Tongtong Wang

    (Faculty of Health and Medical Sciences, University of Adelaide
    Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute)

  • Abdullah M. Ali

    (Columbia University Medical Center)

  • Yan Ma

    (Columbia University Medical Center)

  • Georgette A. Radford

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Laura Vrbanac

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Mari Ichinose

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Samuel Whittle

    (Faculty of Health and Medical Sciences, University of Adelaide
    The Queen Elizabeth Hospital)

  • David J. Hunter

    (University of Sydney)

  • Tamsin R. M. Lannagan

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Nobumi Suzuki

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Jarrad M. Goyne

    (Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute)

  • Hiroki Kobayashi

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Timothy C. Wang

    (Columbia University)

  • David R. Haynes

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Danijela Menicanin

    (Faculty of Health and Medical Sciences, University of Adelaide)

  • Stan Gronthos

    (Faculty of Health and Medical Sciences, University of Adelaide
    University of Adelaide)

  • Daniel L. Worthley

    (Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute
    Colonoscopy Clinic)

  • Susan L. Woods

    (Faculty of Health and Medical Sciences, University of Adelaide
    Precision Cancer Medicine Theme, South Australian Health and Medical Research Institute)

  • Siddhartha Mukherjee

    (Columbia University Medical Center)

Abstract

Osteoarthritis (OA) is characterised by an irreversible degeneration of articular cartilage. Here we show that the BMP-antagonist Gremlin 1 (Grem1) marks a bipotent chondrogenic and osteogenic progenitor cell population within the articular surface. Notably, these progenitors are depleted by injury-induced OA and increasing age. OA is also caused by ablation of Grem1 cells in mice. Transcriptomic and functional analysis in mice found that articular surface Grem1-lineage cells are dependent on Foxo1 and ablation of Foxo1 in Grem1-lineage cells caused OA. FGFR3 signalling was confirmed as a promising therapeutic pathway by administration of pathway activator, FGF18, resulting in Grem1-lineage chondrocyte progenitor cell proliferation, increased cartilage thickness and reduced OA. These findings suggest that OA, in part, is caused by mechanical, developmental or age-related attrition of Grem1 expressing articular cartilage progenitor cells. These cells, and the FGFR3 signalling pathway that sustains them, may be effective future targets for biological management of OA.

Suggested Citation

  • Jia Q. Ng & Toghrul H. Jafarov & Christopher B. Little & Tongtong Wang & Abdullah M. Ali & Yan Ma & Georgette A. Radford & Laura Vrbanac & Mari Ichinose & Samuel Whittle & David J. Hunter & Tamsin R. , 2023. "Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42199-1
    DOI: 10.1038/s41467-023-42199-1
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