Abstract:
Osteoporotic patients have lower bone mass due
to increased bone resorption by osteoclasts. The aim of this
study was to investigate the cytotoxic and antiosteoclastogenic
effects of geraniol, a natural monoterpene
on human CD14+ monocytes (ex vivo) and murine
RAW264.7 macrophages (in vitro) using alamar blue and
tartrate resistant acid phosphatase staining respectively. The
anti-osteoclastogenic activity of geraniol was further
explored by analyzing its effects on actin ring formation and
bone resorptive function of osteoclasts. Geraniol significantly
(p < 0.001) inhibited osteoclast formation in
CD14+ monocytes and RAW264.7 macrophages without
cytotoxicity. Moreover, reduced osteoclastogenesis in these
cells led to an arrest in actin ring formation and diminished
bone resorption. Analysis of underlying molecular
mechanisms revealed that geraniol alleviated NF-kB activity,
an indispensable upstream modulator of osteoclast formation.
Furthermore, expression of key osteoclastogenic
genes such as dendritic cell-specific transmembrane protein
(DC-STAMP) involved in cell-cell fusion and nuclear factor
of activated T-cells, cytoplasmic, calcineurin-dependent
1 (NFATc1), a master transcription factor essential for osteoclast differentiation was downregulated by geraniol.
These observations indicate that inhibition of osteoclast
differentiation is presumably one of the pharmacological
properties of geraniol.
