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Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2
Author(s) -
Park OkJin,
Kim Jiseon,
Yang Jihyun,
Yun CheolHeui,
Han Seung Hyun
Publication year - 2017
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3137
Subject(s) - muramyl dipeptide , osteoblast , runx2 , rankl , osteoclast , chemistry , bone remodeling , inducer , osteoprotegerin , osteoporosis , microbiology and biotechnology , bone mineral , medicine , endocrinology , receptor , biochemistry , in vitro , biology , activator (genetics) , gene
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.