# Molecular hydrogen suppresses activated Wnt/β-catenin signaling.
> 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


## Abstract

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.

### Mechanism

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.

## Bibliographic

- **Authors**: Lin Y, Ohkawara B, Ito M, Misawa N, Miyamoto K, Takegami Y, et al.
- **Journal**: Sci Rep
- **Year**: 2016 (2016-08-25)
- **PMID**: [27558955](https://pubmed.ncbi.nlm.nih.gov/27558955/)
- **DOI**: [10.1038/srep31986](https://doi.org/10.1038/srep31986)
- **PMC**: [PMC5001535](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5001535/)
- **Study type**: in vitro study
- **Delivery route**: mixed routes
- **Effect reported**: positive

## Delivery context

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).

## Safety notes

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:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 27558955. https://h2-papers.org/en/papers/27558955
> **Source**: PubMed PMID [27558955](https://pubmed.ncbi.nlm.nih.gov/27558955/)