RAW264.7細胞におけるH2によるRANKL誘導破骨細胞分化抑制：ROS産生抑制とMAPK・AKT・NF-κB経路の不活性化
Using murine RAW264.7 cells and bone marrow macrophages (BMMs), this study examined how H2 affects RANKL-driven osteoclast differentiation. H2 exposure blocked osteoclast formation and resorption pit development induced by RANKL. Expression of osteoclast-specific markers—including TRAP, calcitonin receptor, cathepsin K, MMP-9, carbonic anhydrase II, and vacuolar H+-ATPase—was reduced at the mRNA level. H2 also decreased intracellular and mitochondrial ROS, suppressed NADPH oxidase activity, downregulated Rac1 and Nox1, and promoted Nrf2 nuclear translocation along with heme oxygenase-1 activity. Downstream signaling analysis revealed reduced NFATc1 and c-Fos expression, diminished NF-κB activation, and attenuated phosphorylation of p38, ERK, JNK, and AKT following RANKL stimulation. These findings indicate that H2 interferes with osteoclastogenesis through coordinated suppression of ROS generation and multiple pro-osteoclastic signaling cascades.
H2 reduces intracellular and mitochondrial ROS by suppressing NADPH oxidase, Rac1, and Nox1, while enhancing Nrf2/HO-1 signaling. Concurrently, it inactivates NF-κB, p38/ERK/JNK MAPK, and AKT pathways, collectively blocking RANKL-induced osteoclast differentiation.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/24196871