Park Ok-Jin, Kim Jiseon, Yang Jihyun, Yun Cheol-Heui, Han Seung Hyun
Department of Oral Microbiology and Immunology, DRI, and BK21 Plus Program, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
Department of Agricultural Biotechnology, World Class University Biomodulation Major and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
J Bone Miner Res. 2017 Jul;32(7):1455-1468. doi: 10.1002/jbmr.3137. Epub 2017 Apr 27.
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.
从肠道微生物群释放的肽聚糖片段可被输送至骨髓并影响骨代谢。我们研究了胞壁酰二肽（MDP）对骨代谢的调节作用，MDP是肽聚糖的一个共同结构单元。在给予MDP的小鼠中，观察到通过增强骨形成而增加了骨密度和矿物质密度。值得注意的是，在RANKL诱导的骨质疏松小鼠模型中，MDP预处理或后处理减轻了骨丢失。MDP通过激活Runx2直接增强成骨细胞分化和骨形成基因表达。尽管没有直接作用，但MDP通过下调RANKL/骨保护素（OPG）比值间接减弱破骨细胞分化。MDP增加了MDP受体Nod2的表达，并且在Nod2缺乏时不会发生MDP诱导的骨形成和成骨细胞激活。其他Nod2配体也像MDP一样通过诱导Runx2增加骨形成。总之，我们认为MDP是一种新型的骨形成诱导剂，可能成为预防骨质疏松症的新治疗分子。©2017美国骨与矿物质研究学会。
