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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Liu, Rui Zhong, Yuping Chen, Rui Chen, Shiyi Huang, Yazhu Liu, Huan |
| Abstract | Multiple myeloma is characterized by osteolytic lesions caused by reduced bone formation and activated bone resorption. An important feature of myeloma is a failure of bone healing after successful treatment. In this work, clinical studies indicated a highly positive correlation between bone marrow bacteria abundance and bone lesion numbers of myeloma patients in complete remission. Coculture experiments demonstrated that marrow Escherichia coli (E. coli) promotes osteoclast differentiation and inhibits osteoblast differentiation. Mechanism studies showed that E. coli lipopolysaccharides (LPS) activated NF-κB p65 signaling and reduced phosphorylated smad1/5/9 binding ability with RUNX2 promoter, leading to decreased RUNX2 expression in osteoblast progenitors. Additionally, LPS enhanced phosphorylated NF-κB p65 binding ability with NFATc1 promoter, leading to increased NFATc1 expression in osteoclast progenitors. In vivo studies revealed E. coli contributes to osteolytic bone lesion, and elimination of E. coli infection assists healing of bone lesion in mouse model of myeloma in complete remission. These findings establish a heretofore unrecognized effect for E. coli in the genesis of myeloma bone disease and suggest a new treatment strategy. |
| Related Links | https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-021-03187-5.pdf |
| Ending Page | 10 |
| Page Count | 10 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14795876 |
| DOI | 10.1186/s12967-021-03187-5 |
| Journal | Journal of Translational Medicine |
| Issue Number | 1 |
| Volume Number | 20 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2022-01-06 |
| Access Restriction | Open |
| Subject Keyword | Biomedicine Medicine Public Health Escherichia coli Multiple myeloma Bone lesion Lipopolysaccharides Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biochemistry, Genetics and Molecular Biology Medicine |
| Journal Impact Factor | 6.1/2023 |
| 5-Year Journal Impact Factor | 6.3/2023 |
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