Research ArticleOsteoarthritis

FoxO transcription factors modulate autophagy and proteoglycan 4 in cartilage homeostasis and osteoarthritis

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Science Translational Medicine  14 Feb 2018:
Vol. 10, Issue 428, eaan0746
DOI: 10.1126/scitranslmed.aan0746

Clever as a FoxO

FoxO proteins are transcription factors that regulate autophagy, metabolism, and aging. Matsuzaki et al. investigated the role of different FoxO in cartilage development, homeostasis, and degeneration during osteoarthritis. Cartilage was thicker and chondrocytes were more proliferative in young mice lacking FoxO1/3/4 in cartilage. Chondrocyte-specific FoxO-deficient mice exhibited worse arthritis with aging and increased cartilage degradation in response to surgically induced arthritis; they also expressed less lubricin, a protein that helps reduce friction in joints. FoxO1 and autophagy-related genes were reduced in human chondrocytes from patients with osteoarthritis, and restoring FoxO1 expression reduced inflammatory cytokines and up-regulated lubricin. This study suggests that FoxO factors could be targets for therapy in osteoarthritis.