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Reversal of the diabetic bone signature with anabolic therapies in mice

Bone Research 2023年第2期11卷 328-339页

作者： Silvia Marino Nisreen Akel Shenyang Li Meloney Cregor Meghan Jones Betiana Perez gaston troncoso Jomeeka Meeks Scott Stewart Amy YSato Intawat Nookaew Teresita Bellido Department of Physiology and Cell Biology University of Arkansas for Medical SciencesLittle RockARUSA Central Arkansas Veterans Healthcare System John L.Mc Clellan Little RockLittle RockARUSA Department of Biostatistics University of Arkansas for Medical SciencesLittle RockARUSA Department of Biomedical Informatics University of Arkansas for Medical SciencesLittle RockARUSA Winthrop P.Rockefeller Cancer Institute University of Arkansas for Medical SciencesLittleRockARUSA

The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood;and antiresorptive agents,the current standard of care,do not restore the weakened bone ***,we reveal the diabetic bone signature in mice at the tissue,cell,and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct *** decreased bone mineral density(BMD)and bone formation,damaged microarchitecture,increased porosity of cortical bone,and compromised bone ***(PTH),abaloparatide(ABL),and romosozumab/anti-sclerostin antibody(Scl-Ab)all restored BMD and corrected the deteriorated bone ***,PTH and more potently ABL induced similar responses at the tissue and gene signature levels,increasing both formation and resorption with positive balance towards bone *** contrast,Scl-Ab increased formation but decreased *** agents restored bone architecture,corrected cortical porosity,and improved mechanical properties of diabetic bone;and ABL and Scl-Ab increased toughness,a fracture resistance ***,all agents increased bone strength over the healthy controls even in the presence of severe *** findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease and suggest the need for revisiting the approaches for the treatment of bone fragility in diabetes.

关键词： signature porosity corrected

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