SOX9
SOX9 is the master transcription factor of cartilage cells, the protein that keeps a chondrocyte working as a chondrocyte by switching on cartilage genes. Falling SOX9 is a sign that cartilage cells are drifting away from their normal role.
Also called SRY-box transcription factor 9.
In osteoarthritis, chondrocytes shift towards lower SOX9 and higher levels of cartilage-cutting enzymes such as MMP13 and ADAMTS5 (Rong 2019). In cells from healthy human cartilage, hydrogen peroxide, the inflammatory signal IL-1 beta and calcium crystals each lowered SOX9 and raised those enzymes (Rong 2019).
SOX9 is also tied to glutathione. In growth-plate cartilage during bone development, SOX9 raised the cells' glutamine uptake, and glutathione made from that glutamine kept reactive oxygen species in check (Stegen 2020). In mouse cartilage cells exposed to an inflammatory signal, dihydrolipoic acid lessened the fall in SOX9 (Chen 2026).
Sources
- Rong J, Zhu M, Munro J et al. Altered expression of the core circadian clock component PERIOD2 contributes to osteoarthritis-like changes in chondrocyte activity. Chronobiol Int 2019.
- Stegen S, Rinaldi G, Loopmans S et al. Glutamine Metabolism Controls Chondrocyte Identity and Function. Dev Cell 2020.
- Chen Y, Fang J, Zhou Z et al. Dihydrolipoic acid suppresses ferroptosis in chondrocytes to ameliorate the progression of osteoarthritis by modulating the FOXO1/TXNIP signaling pathway. Free Radic Biol Med 2026.
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