分子状水素によるWnt/β-カテニンシグナル活性化の抑制機序とその骨関節炎への影響
This study investigated how molecular hydrogen (H2) modulates intracellular signaling pathways. H2 was found to downregulate aberrantly activated Wnt/β-catenin signaling by enhancing phosphorylation and subsequent degradation of β-catenin. Complete GSK3 inhibition or mutations at CK1- and GSK3-phosphorylation sites on β-catenin eliminated this effect. H2 did not alter GSK3-mediated phosphorylation of glycogen synthase, suggesting no direct action on GSK3 itself. Knockdown of APC or Axin1, key components of the β-catenin destruction complex, also abolished H2-mediated suppression. In human osteoarthritis chondrocytes, H2 reduced Wnt/β-catenin activation. In a surgically induced rat osteoarthritis model, oral hydrogen-rich water intake showed a tendency to reduce cartilage degradation, associated with attenuated β-catenin accumulation. These findings identify Wnt/β-catenin pathway modulation as a molecular basis for some of the protective effects attributed to H2.
H2 promotes phosphorylation and proteasomal degradation of β-catenin through the destruction complex comprising CK1, GSK3, APC, and Axin1, thereby suppressing aberrant Wnt/β-catenin pathway activation without directly modifying GSK3 kinase activity.
This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).
See also:
https://h2-papers.org/en/papers/27558955