Modulating Cellular Bioenergetics to Improve Skeletal Health
Modulating Cellular Bioenergetics to Improve Skeletal Health
批准号:
10527457
负责人:
Elizabeth Rendina-Ruedy
金额:
$22.03万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-07-10 至 2024-05-31
关键词:
AddressAdenosine TriphosphateAdipose tissueAdultAdverse eventAffectAgeAge-Related OsteoporosisAnabolic AgentsAreaBioenergeticsBiologicalBiological AssayBiological ModelsBiologyBolus InfusionBone DensityBone MarrowCellsClinicalDataDevelopmentDietary Fatty AcidDoseEffectivenessEnergy SupplyExperimental ModelsFDA approvedFatty AcidsFemurFinancial HardshipForteoFractureGene Expression ProfileGoalsHealthHistologyHormonesIn VitroIncidenceKineticsLate-Onset DisorderLeadLipidsLongevityMass Spectrum AnalysisMeasurementMetabolic PathwayMetabolismMethodologyMethodsMitochondriaMonitorMusMusculoskeletalOleic AcidsOsteoblastsOsteogenesisOsteopeniaOsteoporosisOsteoporoticOutcomeOxygen ConsumptionPTH geneParathyroid glandPatientsPersonsPharmaceutical PreparationsPharmacologic SubstancePhysiologicalPopulationPopulations at RiskPostmenopausal OsteoporosisPreparationPriceProductionProteinsPublic HealthQuality of lifeResearchRespirationSample SizeSamplingStimulusStromal CellsTestingTherapeuticTransfectionTranslatingVisionWorkWorkloadX-Ray Computed Tomographybasebiomechanical testbonebone cellbone fragilitybone healthbone massbone metabolismcell typecombatcomorbiditycostefficacy testingexperimental studyfatty acid metabolismfatty acid oxidationfatty acid supplementationfracture riskhigh rewardhormone therapyimprovedin vivoin vivo Modellipid metabolismluminescencenovelnutritionosteoporosis with pathological fractureoxidationpreventprimary outcomeprogramsresponsesecondary outcomeside effectskeletalspine bone structuretool
中文摘要
项目摘要/摘要
英文摘要
PROJECT SUMMARY/ ABSTRACT
The long-term goal of my research program is to develop a comprehensive understanding of how metabolic
pathways impact bone health. Consistent with this goal, our vision is to apply strategies to identify novel
biological mechanisms, which lead to the development of new treatments that can improve the quality of life for
patients with bone fragility.
Osteoporosis and osteopenia are late-onset diseases affecting a staggering 54 million people in the U.S
addition to the financial burden, osteoporosis-related fractures often lead to multiple comorbidities which
significantly reduce longevity. While anabolic agents that increase bone formation, such as parathyroid
.
In
hormone (PTH), have aided in the management of osteoporosis, patients still experience adverse side-effects.
Therefore, continued development of refined therapeutic options is necessary. Relative to this, the current
project aims to harness PTH’s ability to modulate osteoblast bioenergetic capacity to promote bone formation
by supplying energy fatty acid substrates to meet this demand. Targeting metabolic pathways in bone cells is a
highly provocative tool that can be applied to combat various musculoskeletal conditions which lead to
increased fracture incidence (i.e., post-menopausal osteoporosis and age-related osteoporosis). Within this
scope, the current project aims to explore the osteo-anabolic effects of intermittent parathyroid hormone (iPTH)
via modulation of lipid metabolism on cells within the skeletal niche. Therefore, the overarching hypothesis is
that the osteoanabolic actions of iPTH can be enhanced by supplying osteoblasts with exogenous fatty acids.
This hypothesis will be tested in two specific aims. The first aim will utilize in vivo model systems to determine
whether manipulation in the availability of exogenous fatty acids influences iPTH-induced bone formation. The
second aim will further demonstrate that PTH-induced alterations in osteoblast activity rely on increased
adenosine triphosphate (ATP) production via fatty acid oxidation using a novel in vitro method. This project is
expected to have substantial health-related influence. Specifically, data generated from this project are likely to
translate directly to improve clinical outcomes by (1) identifying a novel bone anabolic mechanism, (2) aid in
the optimization of dosing strategy and/or efficacy of a current FDA-approved bone anabolic agent to prevent
osteoporotic-related fracture, as well as (3) lead to the identification of other pharmaceutical therapies
exploiting similar mechanisms, all of which are directly related to improving musculoskeletal health.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Modulating Cellular Bioenergetics to Improve Skeletal Health
-
批准号:10661806
-
项目类别:
-
资助金额:$19.03万
-
财政年份:2022
-
负责人:Elizabeth Rendina-Ruedy
-
依托单位:
Impaired Lipophagy and Lipid Droplet Accumulation in Osteoblasts
-
批准号:10619139
-
项目类别:
-
资助金额:$6.16万
-
财政年份:2022
-
负责人:Elizabeth Rendina-Ruedy
-
依托单位:
Parathyroid hormone (PTH) modulates lipid metabolism in the skeletal niche
-
批准号:10438842
-
项目类别:
-
资助金额:$42.17万
-
财政年份:2020
-
负责人:Elizabeth Rendina-Ruedy
-
依托单位:
Parathyroid hormone (PTH) modulates lipid metabolism in the skeletal niche
-
批准号:10677565
-
项目类别:
-
资助金额:$42.15万
-
财政年份:2020
-
负责人:Elizabeth Rendina-Ruedy
-
依托单位:
Parathyroid hormone (PTH) modulates lipid metabolism in the skeletal niche
-
批准号:10265544
-
项目类别:
-
资助金额:$42.19万
-
财政年份:2020
-
负责人:Elizabeth Rendina-Ruedy
-
依托单位:
Parathyroid hormone (PTH) modulates lipid metabolism in the skeletal niche
-
批准号:10093413
-
项目类别:
-
资助金额:$44.03万
-
财政年份:2020
-
负责人:Elizabeth Rendina-Ruedy
-
依托单位:
Impaired Lipophagy and Lipid Droplet Accumulation in Osteoblasts
-
批准号:10192660
-
项目类别:
-
资助金额:$9.34万
-
财政年份:2019
-
负责人:Elizabeth Rendina-Ruedy
-
依托单位:
Impaired Lipophagy and Lipid Droplet Accumulation in Osteoblasts
-
批准号:9761431
-
项目类别:
-
资助金额:$9.51万
-
财政年份:2019
-
负责人:Elizabeth Rendina-Ruedy
-
依托单位:
海外基金