Transcriptome analysis of hydrogen inhibits osteoclastogenesis of mouse bone marrow mononuclear cells

Hydrogen (H₂) is a major biodegradation product of implanted magnesium (Mg) alloys that are commonly used in the healing of bone fractures. Our earlier study showed that H₂ can inhibit mouse bone marrow mononuclear cell (BMMC) osteoclastogenesis during the differentiation of these cells into osteoclasts, thereby facilitating fracture healing. However, the way by which H₂ inhibits osteoclastogenesis remains to be elucidated. The present study used RNA-sequencing to study the transcriptome of H₂-exposed BMMCs in an osteoclast-induced environment and identified the target genes and signaling pathways through which H₂ exerts its biological effects. Several upregulated genes were identified: Fos, Dusp1, Cxcl1, Reln, Itga2b, Plin2, Lif, Thbs1, Vegfa and Gadd45a. Several downregulated genes were also revealed: Hspa1b, Gm4951, F830016B08Rik, Fads2, Hspa1a, Slc27a6, Cacna1b, Scd2, Lama3 and Col4a5. These differentially expressed genes were mainly involved in osteoclast differentiation cascades, as well as PI3K-AKT, Forkhead box O (FoxO), MAPK, peroxisome proliferator-activated receptor (PPAR), TNF, TGF-β, JAK-STAT, RAS, VEGF, hypoxia-inducible factor (HIF-1) and AMPK signaling pathways. In summary, the present study revealed the key genes and signaling pathways involved in the H₂-mediated inhibition of osteoclastogenesis, thereby providing a theoretical basis for the significance of H₂ and an experimental basis for the application of Mg alloys in the treatment of osteoporosis.