Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2.
Peptidoglycan fragments released from gut microbiota can be delivered to the bone marrow and affect bone metabolism. We investigated the regulation of bone metabolism by muramyl dipeptide (MDP), which is a shared structural unit of peptidoglycans. Increased bone and mineral density by enhanced bone formation were observed in mice administered with MDP. Remarkably, pretreatment or posttreatment with MDP alleviated bone loss in RANKL-induced osteoporosis mouse models. MDP directly augmented osteoblast differentiation and bone-forming gene expression by Runx2 activation. Despite no direct effect, MDP indirectly attenuated osteoclast differentiation through downregulation of the RANKL/osteoprotegerin (OPG) ratio. MDP increased the expression of the MDP receptor, Nod2, and MDP-induced bone formation and osteoblast activation did not occur during Nod2 deficiency. Other Nod2 ligands also increased bone formation through the induction of Runx2, as MDP did. In conclusion, we suggest that MDP is a novel inducer of bone formation that could potentially be a new therapeutic molecule to protect against osteoporosis. © 2017 American Society for Bone and Mineral Research.
Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Ok-Jin
OJ
Park
Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Jiseon
J
Kim
Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Jihyun
J
Yang
Department of Agricultural Biotechnology, World Class University Biomodulation Major and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
Cheol-Heui
CH
Yun
Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Seung Hyun
SH
Han
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000737:chemistry / Q000494:pharmacology*; D020816:Amino Acid Motifs; D000818:Animals; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects*; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000235:genetics; D010457:Peptidoglycan / Q000737:chemistry*; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics
D050659:Core Binding Factor Alpha 1 Subunit; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D053244:Osteoprotegerin; D010457:Peptidoglycan; D053245:RANK Ligand; C493716:Runx2 protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D000119:Acetylmuramyl-Alanyl-Isoglutamine
BONE FORMATION; MURAMYL DIPEPTIDE; OSTEOBLAST; RUNX2