Inhibitory effect of minocycline on osteoclastogenesis in mouse bone marrow cells

Arch Oral Biol. 2011 Sep;56(9):924-31. doi: 10.1016/j.archoralbio.2011.02.002. Epub 2011 Mar 5.


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)(2)D(3) 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 10μM), such as MINO, tetracycline hydrochloride (TC), oxytetracycline hydrochloride (OXT) or doxycycline (DOXY) in the presence of 1α,25(OH)(2)D(3) (10nM) or s-RANKL (20ng/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)(2)D(3) 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 (0.25-20μM and 2-50μM, respectively) for 24h.

Results: MINO, TC, OXT or DOXY inhibited 1α,25(OH)(2)D(3)-induced osteoclast-like cell formation in mouse BMCs dose dependently. MINO suppressed 1α,25(OH)(2)D(3)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Calcitriol / pharmacology
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Down-Regulation
  • Isoenzymes / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Minocycline / pharmacology*
  • NFATC Transcription Factors / biosynthesis*
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • RANK Ligand / pharmacology
  • Rabbits
  • Tartrate-Resistant Acid Phosphatase


  • Anti-Bacterial Agents
  • Isoenzymes
  • NFATC Transcription Factors
  • RANK Ligand
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
  • Calcitriol
  • Minocycline