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| 1 | DMP1 prevents osteocyte alterations,FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease显示文摘During chronic kidney disease (CKD),alterations in bone and mineral metabolism include increased production of the hormone fibroblast growth factor 23 (FGF23) that may contribute to cardiovascular mortality.The osteocyte protein dentin matrix protein 1 (DMP1) reduces FGF23 and enhances bone mineralization,but its effects in CKD are unknown.We tested the hypothesis that DMP1 supplementation in CKD would improve bone health,prevent FGF23 elevations and minimize consequent adverse cardiovascular outcomes.We investigated DMP1 regulation and effects in wild-type (WT) mice and the Col4a3^-/- mouse model of CKD.Col4a3^-/- mice demonstrated impaired kidney function,reduced bone DMP1 expression,reduced bone mass,altered osteocyte morphology and connectivity,increased osteocyte apoptosis,increased serum FGF23,hyperphosphatemia,left ventricular hypertrophy (LVH),and reduced survival.Genetic or pharmacological supplementation of DMP1 in Col4a3^-/- mice prevented osteocyte apoptosis,preserved osteocyte networks,corrected bone mass,partially lowered FGF23 levels by attenuating NFAT-induced FGF23 transcription,and further increased serum phosphate.Despite impaired kidney function and worsened hyperphosphatemia,DMP1 prevented development of LVH and improved Col4a3^-/- survival.Our data suggest that CKD reduces DMP1 expression,whereas its restoration represents a potential therapeutic approach to lower FGF23 and improve bone and cardiac health in CKD. | Corey Dussold Claire Gerber Samantha White Xueyan Wang Lixin Qi Connor Francis Maralee Capella Guillaume Courbon Jingya Wang Chaoyuan Li Jian Q. Feng Tamara Isakova Myles Wolf Valentin David Aline Martin | 2019 | Bone Research2019，7，2： | 4 |
| 2 | Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease显示文摘Bone-produced fibroblast growth factor 23(FGF23)increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease(CKD).Neutrophil gelatinase-associated lipocalin(NGAL or lipocalin 2;LCN2 the murine homolog)is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD progression.We investigated bone FGF23 regulation by circulating LCN2.At 23 weeks,Col4a3KO mice showed impaired kidney function,increased levels of kidney and serum LCN2,increased bone and serum FGF23,anemia,and left ventricular hypertrophy(LVH).Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum FGF23.Lcn2 deletion specifically prevented FGF23 elevations in response to inflammation,but not iron deficiency or phosphate,and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone cells.These results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in CKD.LCN2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD. | Guillaume Courbon Connor Francis Claire Gerber Samantha Neuburg Xueyan Wang Emily Lynch Tamara Isakova Jodie LBabitt Myles Wolf Aline Martin Valentin David | 2021 | Bone Research2021，9，3： | 4 |
| 3 | Vitamin D Deficiency and Risk of Cardiovascular Disease显示文摘 | Thomas J. Wang Michael J. Pencina Sarah L. Booth Paul F. Jacques Erik Ingelsson Katherine Lanier Emelia J. Benjamin Ralph B. D?Agostino Myles Wolf Ramachandran S. Vasan | 2008 | Circulation2008，，4： | 2 |
| 4 | First - Trimister C - reactive protein and subsequent gestattional diabetes 显示文摘 | Myles Wolf Karen Vossen - Smimakis Laura Sandier | 2003 | Diabetes Care2003，26，3： | 1 |
| 5 | First-Trimister C reactive protein and subsequent gestattional di abetes显示文摘 | Myles Wolf Karen Vossen-Smirnakis Laura Sandier | 2003 | Diabetes Care2003，26，3： | 1 |
| 6 | Activated injectable vitamin D and hemodialysis survival:a historical cohort study显示文摘 | Ming Teng Myles Wolf Ofsthun MN | | 0，，： | 1 |
| 7 | First-Trimister C-reactive protein and subsequent gestattional diabetes显示文摘 | Myles Wolf Karen Vossen-Smimakis Laura Sandler | 2003 | Diabetes Care2003，26，3： | 1 |
| 8 | Obe- sity and preeelampsia: The potential role of inflammation 显示文摘 | Wolf Myles MD Kettyle Elizabeth CNM | 2001 | ObstetGynecol2001，98，11： | 1 |
| 9 | Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women显示文摘 | Myles Wolf Todd A Koch David B Bregman | 2013 | J Bone Miner Res2013，，8： | 1 |
| 10 | Vitamin D Deficiency, Inflammation, and Albuminuria in Chronic Kidney Disease: Complex Interactions显示文摘 | Tamara Isakova Orlando M. Gutiérrez Neha M. Patel Dennis L. Andress Myles Wolf Adeera Levin | 2011 | Journal of Renal Nutrition2011，，4： | 1 |
| 11 | First -Trimister C-creative protein and subsequent gestational diabetes 显示文摘 | Myles Wolf Karen Vossen-Smimakis Laura Sandler | 2003 | Diabetes Care2003，26，3： | 1 |
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