Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis

Won Y, Shin Y, Chun CH, et al. · Annals of the Rheumatic Diseases

The zinc-buffering metallothioneins induced by the zinc-ZIP8-MTF1 axis turned out to be double-edged: deleting Mt1/Mt2 worsened cartilage destruction via chondrocyte apoptosis, while chronic MT2 overexpression itself upregulated matrix-degrading enzymes and drove OA — zinc handling in cartilage is a tightly balanced system, not a more-is-better one.

Population

Mouse surgical-OA and adenoviral gene-delivery models; human OA cartilage; cultured chondrocytes

Intervention

Overexpression or knockout of metallothioneins MT1/MT2, downstream targets of the zinc-ZIP8-MTF1 axis

Comparator

Wild-type mice / control-infected chondrocytes

Limitations

Same group as the 2014 Cell paper (full text read); mouse and in-vitro only; no dietary zinc exposure tested.