Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis.

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. © 2023. The Author(s).

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 M Lannagan, Nobumi Suzuki, Jarrad M Goyne, Hiroki Kobayashi, Timothy C Wang, David R Haynes, Danijela Menicanin, Stan Gronthos, Daniel L Worthley, Susan L Woods, Siddhartha Mukherjee. Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis. Nature communications. 2023 Oct 31;14(1):6909

Mesh Tags

Substances

PMID: 37907525

search → result