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

Hydrogen (H(2)) 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 H(2) 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 H(2) inhibits osteoclastogenesis remains to be elucidated. The present study used RNA-sequencing to study the transcriptome of H(2)-exposed BMMCs in an osteoclast-induced environment and identified the target genes and signaling pathways through which H(2) 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 H(2)-mediated inhibition of osteoclastogenesis, thereby providing a theoretical basis for the significance of H(2) and an experimental basis for the application of Mg alloys in the treatment of osteoporosis.