Regulation of the catabolic cascade in osteoarthritis by the zinc-ZIP8-MTF1 axis

Kim JH, Jeon J, Shin M, et al. · Cell

The zinc importer ZIP8 was specifically upregulated in OA cartilage of humans and mice; zinc influx through ZIP8 upregulated matrix-degrading enzymes (MMP3, MMP9, MMP12, MMP13, ADAMTS5), ectopic ZIP8 expression in mouse cartilage caused OA-like destruction, and Zip8 knockout suppressed surgically induced OA — casting chondrocyte zinc influx as a catabolic driver, not a nutrient benefit.

Population

Human OA cartilage specimens plus mouse surgical-OA models and cultured chondrocytes

Intervention

Genetic gain/loss of function of the zinc importer ZIP8 and the zinc-dependent transcription factor MTF1

Comparator

Wild-type mice / control chondrocytes

Limitations

Genetic manipulation in mice and tissue immunostaining, not a feeding study — it does not test oral zinc intake or any dose; landmark paper (Cell) from a single group, with the mechanism later extended by the same lab.