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Published on: December 10, 2010
Muramyl dipeptide enhances lipopolysaccharide-induced osteoclast formation and bone resorption through increased
Masahiko Ishida1, Hideki Kitaura1, Keisuke Kimura1
1Division of Orthodontics and Dentofacial Orthopedics, Department of Translational Medicine, Tohoku University Graduate School of Dentistry, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Abstract:
Lipopolysaccharide (LPS) is bacterial cell wall component capable of inducing osteoclast formation and pathological bone resorption. Muramyl dipeptide (MDP), the minimal essential structural unit responsible for the immunological activity of peptidoglycans, is ubiquitously expressed by bacterium. In this study, we investigated the effect of MDP in LPS-induced osteoclast formation and bone resorption. LPS was administered with or without MDP into the supracalvariae of mice. The number of osteoclasts, the level of mRNA for cathepsin K and tartrate-resistant acid phosphatase (TRAP), the ratio of the bone destruction area, the level of tartrate-resistant acid phosphatase form 5b (TRACP 5b), and C-terminal telopeptides fragments of type I collagen as a marker of bone resorption in mice administrated both LPS and MDP were higher than those in mice administrated LPS or MDP alone. On the other hand, MDP had no effect on osteoclastogenesis in parathyroid hormone administrated mice. MDP enhanced LPS-induced receptor activator of NF-κB ligand (RANKL) expression and Toll-like receptor 4 (TLR4) expression in vivo and in stromal cells in vitro. MDP also enhanced LPS-induced mitogen-activated protein kinase (MAPK) signaling, including ERK, p38, and JNK, in stromal cells. These results suggest that MDP might play an important role in pathological bone resorption in bacterial infection diseases.
Insights
Muramyl dipeptide (MDP) exacerbates lipopolysaccharide (LPS)-induced bone resorption by increasing osteoclast formation. MDP enhances LPS effects on bone destruction, suggesting a role in bacterial infection diseases.
Area of Science:
- Immunology
- Cell Biology
- Bone Biology
Background:
- Lipopolysaccharide (LPS) from bacterial cell walls induces osteoclast formation and bone resorption.
- Muramyl dipeptide (MDP) is a key component of bacterial peptidoglycans with immunological activity.
Purpose of the Study:
- To investigate the effect of MDP on LPS-induced osteoclast formation and bone resorption.
- To elucidate the molecular mechanisms underlying MDP's influence on LPS-induced bone pathology.
Main Methods:
- Administration of LPS with or without MDP into mouse supracalvariae.
- Quantification of osteoclast numbers, bone destruction area, and bone resorption markers (TRACP 5b, CTX-I).
- Analysis of mRNA expression for cathepsin K and TRAP, and evaluation of RANKL, TLR4, and MAPK signaling pathways.
Main Results:
- MDP significantly increased LPS-induced osteoclast formation, bone resorption markers, and bone destruction.
- MDP enhanced LPS-induced expression of RANKL and TLR4 in vivo and in vitro.
- MDP potentiated LPS-induced MAPK signaling (ERK, p38, JNK) in stromal cells.
Conclusions:
- MDP amplifies LPS-induced osteoclastogenesis and bone resorption.
- MDP's effects are mediated through enhanced RANKL, TLR4, and MAPK signaling.
- MDP may contribute significantly to pathological bone loss in bacterial infections.
