Homocysteine causes dysfunction of chondrocytes and oxidative stress through repression of SIRT1/AMPK pathway: A possible link between hyperhomocysteinemia and osteoarthritis

Ma CH, Chiua YC, Wu CH, Jou IM, Tu YK, Hung CH, Hsieh PL, Tsai KL · Redox Biology

The step the betaine hypothesis needs and the only one anybody has taken in cartilage: homocysteine suppressed the SIRT1/AMPK/PGC-1alpha axis in chondrocytes, causing mitochondrial dysfunction, oxidative stress and apoptosis, and raising NF-kB, COX-2, IL-8 and MMP-13; the same pathway changes appeared in cartilage of animals fed into hyperhomocysteinemia.

Population

Cultured chondrocytes plus a diet-induced hyperhomocysteinemia animal model

Intervention

Homocysteine exposure; dietary induction of high homocysteine

Comparator

Untreated chondrocytes and normal-diet animals

Limitations

Cells and a diet model rather than a supplement trial — it shows that raising homocysteine harms chondrocytes, not that lowering it with betaine helps them; abstract-level appraisal of doses and group sizes.