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

Tests the step the betaine hypothesis needs, 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

Human chondrocytes in culture, plus 12 C57BL mice fed with or without 1% L-methionine in water for 4 months to induce hyperhomocysteinemia

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; six mice per group. Taiwanese public and hospital grants; no conflict declared.