Research Article - Biomedical Research (2025) Volume 36, Issue 4

Inhibitory Effects of Magnesium Hydroxide Nanoparticles on Osteoclast Differentiation via Suppression of RANKL-induced MAPK Signaling

Objectives: Magnesium hydroxide has been reported to promote bone formation; however, its specific effects on osteoclast differentiation remain unclear. This study aimed to investigate the inhibitory effects of magnesium hydroxide nanoparticles (NM80) on osteoclast formation and elucidate the underlying molecular mechanisms.

Methods: Osteoclast differentiation was induced in RAW264.7 cells and mouse bone marrow cells using Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL). The effects of NM80 on Tartrate-Resistant Acid Phosphatase (TRAP)-positive multinucleated cell formation, osteoclast-related gene expression, and MAPK signaling pathway activation were evaluated using TRAP staining, quantitative RT-PCR, and Western blot analysis, respectively.

Results: NM80 significantly reduced RANKL-induced osteoclast formation in both RAW264.7 and bone marrow cells without cytotoxic effects. The mRNA expression of osteoclast-related markers, including cathepsin K, Acp5, Dc-stamp, and Nfatc1, was downregulated. Furthermore, NM80 inhibited the phosphorylation of p38 MAPK and ERK but did not affect JNK activation or IκBα degradation, indicating selective suppression of the MAPK pathway.

Conclusion: Magnesium hydroxide nanoparticles suppress osteoclast differentiation via inhibition of the RANKLinduced MAPK signaling pathway. These findings suggest NM80 as a potential therapeutic agent for bone metabolic diseases.

Author(s):

Soichiro Hikita, Ayaka Koga, Yoshie Nagai-Yoshioka, Ryota Yamasaki, Daisuke Kudo, Dao Nguyen Duy Phuong, Yoshihito Iwamoto, Osamu Takahashi, Masaaki Sasaguri, Manabu Habu, Wataru Ariyoshi

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