(−)‐Epigallocatechin‐3‐
O
‐gallate (
EGCG
), present in green tea, exhibits antioxidant and antiallergy effects.
EGCG
3″Me, a 3‐
O
‐methylated derivative of
EGCG
, has been reported to show similar biological functions; the inhibitory activity of
EGCG
3″Me in a mouse allergy model was more potent than that of
EGCG
, probably due to the efficiency of absorption from the intestine. However, the functional potency of these
EGCG
s is controversial in each disease model. We previously observed that
EGCG
suppressed inflammatory bone resorption and prevented alveolar bone loss in a mouse model of periodontosis. In this study, we examined the role of
EGCG
3″Me in bone resorption using a mouse model of periodontitis. Lipopolysaccharide (
LPS
)‐induced osteoclast formation was suppressed by adding
EGCG
3″Me to cocultures of osteoblasts and bone marrow cells, and
LPS
‐induced bone resorption was also inhibited by
EGCG
3″Me in calvarial organ cultures.
EGCG
3″Me acted on osteoblasts and suppressed prostaglandin E (
PGE
) production, which is critical for inflammatory bone resorption, by inhibiting the expression of
COX
‐2 and
mPGES
‐1, key enzymes for
PGE
synthesis. In osteoclast precursor macrophages,
EGCG
3″Me suppressed
RANKL
‐dependent differentiation into mature osteoclasts. In a mouse model of periodontitis,
LPS
‐induced bone resorption was suppressed by
EGCG
3″Me in organ culture of mouse alveolar bone, and the alveolar bone loss was further attenuated by the treatment of
EGCG
3″Me in the lower gingiva
in vivo
.
EGCG
3″Me may be a potential natural compound for the protection of inflammatory bone loss in periodontitis.