Inhibitory effect of minocycline on osteoclastogenesis in mouse bone marrow cells

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• 作者：Tsuneyasu Nagasawa^a ; Michitsugu Arai^a ; Akifumi Togari ; ^a ; ^{togariaf@dpc.aichi-gakuin.ac.jp"" rel=""nofollow}
• 关键词：Minocycline ; Tetracycline ; Osteoclast ; Osteoclastogenesis ; Bone marrow cells ; RANKL
• 刊名：Archives of Oral Biology
• 出版年：2011
• 出版时间：September 2011
• 年：2011
• 卷：56
• 期：9
• 页码：924-931
• 全文大小：675 K

文摘

Objective

To study the effects of minocycline hydrochloride (MINO) on the formation of tartrate-resistant acid phosphatase (TRAP) staining-positive multinucleated osteoclast-like cells in mouse bone marrow cells (BMCs) treated with 1α,25(OH)₂D₃ or soluble receptor activator of nuclear factor-κB ligand (s-RANKL).

Materials and methods

Mouse BMCs were cultured in alpha-modified minimum essential medium containing foetal calf serum (10 % ) and tetracyclines (2.5, 5 and 10 μM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1α,25(OH)₂D₃ (10 nM) or s-RANKL (20 ng/ml) for 7 days, and the number of TRAP staining-positive osteoclast-like cells was counted. In RNA isolated from BMCs treated with 1α,25(OH)₂D₃ or s-RANKL in the presence or absence of MINO, the expressions of osteoclast differentiation relating to mRNA were analysed by reverse transcription-polymerase chain reaction. Cell viability was examined in mouse BMCs and rabbit osteoclasts treated with MINO (0.25–20 μM and 2–50 μM, respectively) for 24 h.

Results

MINO, TC, OXT or DOXY inhibited 1α,25(OH)₂D₃-induced osteoclast-like cell formation in mouse BMCs dose dependently. MINO suppressed 1α,25(OH)₂D₃-induced up-regulation of mRNA expressions of TRAP, cathepsin K, carbonic anhydrase II, and calcitonin receptor, but not RANKL. MINO inhibited s-RANKL-induced osteoclast-like cell formation and up-regulation of mRNA expressions for nuclear factor of activated T-cells c1 (NFATc1), a key regulator of osteoclast differentiation; however, MINO had no effects on the viability of mouse BMCs and rabbit osteoclasts.

Conclusion

MINO inhibits RANKL-induced osteoclastogenesis via down-regulation of NFATc1 mRNA expression in osteoclast precursor cells.