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Int J Mol Sci ; 22(11)2021 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-34071042

RESUMEN

Osteoporosis is a chronic disease that has become a serious public health problem due to the associated reduction in quality of life and its increasing financial burden. It is known that inhibiting osteoclast differentiation and promoting osteoblast formation prevents osteoporosis. As there is no drug with this dual activity without clinical side effects, new alternatives are needed. Here, we demonstrate that austalide K, isolated from the marine fungus Penicillium rudallenes, has dual activities in bone remodeling. Austalide K inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and improves bone morphogenetic protein (BMP)-2-mediated osteoblast differentiation in vitro without cytotoxicity. The nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), dendritic cell-specific transmembrane protein (DC-STAMP), and cathepsin K (CTSK) osteoclast-formation-related genes were reduced and alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN) (osteoblast activation-related genes) were simultaneously upregulated by treatment with austalide K. Furthermore, austalide K showed good efficacy in an LPS-induced bone loss in vivo model. Bone volume, trabecular separation, trabecular thickness, and bone mineral density were recovered by austalide K. On the basis of these results, austalide K may lead to new drug treatments for bone diseases such as osteoporosis.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Resorción Ósea/prevención & control , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Penicillium/química , Xantenos/uso terapéutico , Animales , Conservadores de la Densidad Ósea/aislamiento & purificación , Conservadores de la Densidad Ósea/farmacología , Resorción Ósea/inducido químicamente , Diferenciación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Sedimentos Geológicos/microbiología , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos ICR , Estructura Molecular , Factores de Transcripción NFATC/biosíntesis , Factores de Transcripción NFATC/genética , Osteoporosis , Penicillium/aislamiento & purificación , Ligando RANK/farmacología , Fosfatasa Ácida Tartratorresistente/antagonistas & inhibidores , Xantenos/aislamiento & purificación , Xantenos/farmacología
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