Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2

Park, Ok-Jin; Kim, Jiseon; Yang, Jihyun; Yun, Cheol‐Heui

doi:10.1002/jbmr.3137

Cited by 21 publications

(24 citation statements)

References 54 publications

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“…The expression of TNFα and the osteoclastogenic factor RANKL in bone was reduced in GF compared to CONV-R WT mice but not in Nod1 −/− or Nod2 −/− mice indicating that the effect of the GM to increase TNFα and RANKL in bone and to reduce bone mass is dependent on both NOD1 and NOD2 signaling. It was recently demonstrated that muramyl dipeptide (MDP), known as a shared structural unit of peptidoglycans from both gram-positive and gram-negative bacteria and a ligand to NOD2, regulates bone mass indicating that the NOD2 signaling pathway is involved in GM effects on bone [ 32 ].…”

Section: Effects Of Gm On Bone Metabolismmentioning

confidence: 99%

Osteomicrobiology: A New Cross-Disciplinary Research Field

Ohlsson

Sjögren

2017

Calcif Tissue Int

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The mutualistic interaction between the gut microbiota (GM) and its host profoundly shapes many aspects of our physiology. The composition and activity of the gut microbiota is modulated by environmental factors such as dietary habits and antibiotic treatments. In rodents, studies demonstrate that the GM is a crucial regulator of bone metabolism and that modulation of the GM composition by probiotic interventions can prevent castration-induced bone loss. Short-term colonization of germ-free mice with GM results in an activation of CD4+T cells, resulting in increased levels of pro-inflammatory cytokines in bone and thereby activation of osteoclastic bone resorption. Besides these immune-mediated effects on bone mass, the GM is involved in nutritional uptake and may, thereby, regulate overall body growth and bone sizes possibly mediated via altered IGF-I levels. We recently introduced a new term “osteomicrobiology” for the rapidly emerging research field of the role of the microbiota in bone health. This research field is aimed to bridge the gaps between bone physiology, gastroenterology, immunology, and microbiology. Future studies will determine if the GM is a novel therapeutic target for osteoporosis and if the GM composition might be used as a biomarker for fracture prediction.

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Section: Effects Of Gm On Bone Metabolismmentioning

confidence: 99%

Osteomicrobiology: A New Cross-Disciplinary Research Field

Ohlsson

Sjögren

2017

Calcif Tissue Int

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“…In addition, the GM also maintains bone homeostasis by regulating calcium absorption-related proteins and modulating tight junction proteins [ 11 , 16 , 17 ]. GM-derived lipopolysaccharide (LPS) and muramyl dipeptide (MDP) indirectly affect osteoclast proliferation and differentiation by inducing an inflammatory response [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Structural and functional changes of gut microbiota in ovariectomized rats and their correlations with altered bone mass

Qin

Hao

et al. 2020

Aging

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As a critical factor involved in the maintenance of physiological homeostasis, the gut microbiota (GM) reportedly plays a key role in bone development. To date, the association between the GM and steroid deficiency-induced osteoporosis remains poorly understood. Forty female Sprague Dawley rats were divided into an ovariectomy (OVX) or control group. We performed 16S rRNA and metagenome sequencing, to compare diversity, taxonomic differences, and functional genes. The GM composition did not change in the control group and the number of operational taxonomic units increased significantly following ovariectomy. Alpha diversity, determined by ACE estimator, CHAO estimator, the Shannon index, and the Simpson index showed an increasing trend after ovariectomy. Samples in the OVX group were well clustered both pre- and post-ovariectomy, as demonstrated by principal coordinate 1 (PC1) and PC2. Functional genes of GM, including those involved in synthesis and metabolism of carbohydrates and nucleotides, microbial structure, and heme, as well as hemin uptake and utilization, increased at the early stage of osteoporosis. We observed that Ruminococcus flavefaciens exhibited the greatest variation in abundance among the GM and this was also associated with osteoclastic indicators and the estrobolome. Specific changes in fecal microbiota are associated with the pathogenesis of steroid deficiency-induced osteoporosis.

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“…They are all upregulated when bone formation is increased. 16 Bone formation and bone resorption of subchondral bone directly affect subchondral bone microstructure.…”

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confidence: 99%

Knee loading repairs osteoporotic osteoarthritis by relieving abnormal remodeling of subchondral bone via Wnt/β‐catenin signaling

Zheng

Ding

et al. 2020

FASEB j.

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Osteoporotic osteoarthritis (OPOA) is a common bone disease mostly in the elderly, but the relationship between Osteoporotic (OP) and osteoarthritis (OA) is complex. It has been shown that knee loading can mitigate OA symptoms. However, its effects on OPOA remain unclear. In this study, we characterized pathological linkage of OP to OA, and evaluated the effect of knee loading on OPOA. We employed two mouse models (OA and OPOA), and conducted histology, cytology, and molecular analyses. In the OA and OPOA groups, articular cartilage was degenerated and Osteoarthritis Research Society International score was increased. Subchondral bone underwent abnormal remodeling, the differentiation of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts and chondrocytes was reduced, and migration and adhesion of pre‐osteoclasts were enhanced. Compared to the OA group, the pathological changes of OA in the OPOA group were considerably aggravated. After knee loading, however, cartilage degradation was effectively prevented, and the abnormal remodeling of subchondral bone was significantly inhibited. The differentiation of BMSCs was also improved, and the expression of Wnt/β‐catenin was elevated. Collectively, this study demonstrates that osteoporosis aggravates OA symptoms. Knee loading restores OPOA by regulating subchondral bone remodeling, and may provide an effective method for repairing OPOA.

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Muramyl Dipeptide, a Shared Structural Motif of Peptidoglycans, Is a Novel Inducer of Bone Formation through Induction of Runx2

Cited by 21 publications

References 54 publications

Osteomicrobiology: A New Cross-Disciplinary Research Field

Osteomicrobiology: A New Cross-Disciplinary Research Field

Structural and functional changes of gut microbiota in ovariectomized rats and their correlations with altered bone mass

Knee loading repairs osteoporotic osteoarthritis by relieving abnormal remodeling of subchondral bone via Wnt/β‐catenin signaling

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