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A Multifunctional Therapeutic Strategy Using P7C3 as A Countermeasure Against Bone Loss and Fragility in An Ovariectomized Rat Model of Postmenopausal Osteoporosis.
Wei, Fei; Hughes, Megan; Omer, Mahmoud; Ngo, Christopher; Pugazhendhi, Abinaya Sindu; Kolanthai, Elayaraja; Aceto, Matthew; Ghattas, Yasmine; Razavi, Mehdi; Kean, Thomas J; Seal, Sudipta; Coathup, Melanie.
Afiliación
  • Wei F; Biionix Cluster, University of Central Florida, Orlando, FL, 82816, USA.
  • Hughes M; School of Biosciences, Cardiff University, Wales, CF10 3AT, UK.
  • Omer M; Biionix Cluster, University of Central Florida, Orlando, FL, 82816, USA.
  • Ngo C; Biionix Cluster, University of Central Florida, Orlando, FL, 82816, USA.
  • Pugazhendhi AS; College of Medicine, University of Central Florida, Orlando, FL, 32827, USA.
  • Kolanthai E; Biionix Cluster, University of Central Florida, Orlando, FL, 82816, USA.
  • Aceto M; Advanced Materials Processing and Analysis Centre, Nanoscience Technology Center (NSTC), University of Central Florida, Orlando, FL, 32826, USA.
  • Ghattas Y; College of Medicine, University of Central Florida, Orlando, FL, 32827, USA.
  • Razavi M; College of Medicine, University of Central Florida, Orlando, FL, 32827, USA.
  • Kean TJ; Biionix Cluster, University of Central Florida, Orlando, FL, 82816, USA.
  • Seal S; College of Medicine, University of Central Florida, Orlando, FL, 32827, USA.
  • Coathup M; Biionix Cluster, University of Central Florida, Orlando, FL, 82816, USA.
Adv Sci (Weinh) ; 11(21): e2308698, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38477537
ABSTRACT
By 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3 (P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)-induced osteoporosis. Results confirm OVX-induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole-body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor-BB and leukemia inhibitory factor, with downregulation of interleukin-1 R6, and receptor activator of nuclear factor kappa-B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor-beta/SMAD, and Wingless-related integration site/be-catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo-osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX-induced bone loss.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovariectomía / Osteoporosis Posmenopáusica / Modelos Animales de Enfermedad Límite: Animals / Female / Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovariectomía / Osteoporosis Posmenopáusica / Modelos Animales de Enfermedad Límite: Animals / Female / Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Alemania