Modulatory effects of silibinin in cell behavior during osteogenic phenotype

Autor(es)

da Costa Fernandes, Celio Jr. ; Veiga, Mariana R. ^[1] ; Serrao Peracoli, Maria Terezinha ^[1] ; Zambuzzi, Willian F. ^[2]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Inst Biosci, Dept Microbiol & Immunol, Botucatu, SP - Brazil

^[2] da Costa Fernandes, Jr., Celio Jr., Sao Paulo State Univ UNESP, Inst Biosci, Lab Bioassays & Cell Dynam, Dept Chem & Biochem, BR-18618970 Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Biochemistry; v. 120, n. 8, p. 13413-13425, AUG 2019.
• Citações Web of Science: 1

Resumo

Natural molecules, such as flavonoid, are very welcome strategies to modulate bone turnover. This prompted us to comprehend better the effect of silibinin on osteoblast metabolism, mainly considering intracellular pathways able to drive cell adhesion to differentiation. By exploring in vitro approaches, our data show a modulatory effect of the silibinin (200 mu g/mL) on the osteoblast intracellular signaling, contributing with decisive pathways governing cell adhesion, differentiation, and further mineralization, recapitulating important stages of osteogenesis. Within the first 24 hours of adhesion (acute stage), osteoblasts respond to silibinin by rearranging their cytoskeleton and start mechanisms responsible to extracellular matrix (ECM) remodeling, which reach intense profile at 28 days of treatment (chronic stage) by favoring matrix metalloproteinases (MMPs-2, and -9) activities, concomitant to mineralizing phenotype. Importantly, silibinin seems to reprogram genes related to inflammatory landscape and significantly upmodulating osteoprotegerin (>25 fold-changes), signaling molecule involved with osteoclastogenesis. Altogether, our results show for the first time that silibinin drives in vitro osteoblast differentiation by requiring specific intracellular signaling. In conjunction, this molecular landscape contributes to understand the effect of silibinin on osteoblasts performance and open novel therapeutic possibilities to silibinin in bone disorders, such as osteoporosis. (AU)

• Processo FAPESP: 14/22689-3 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo
• Beneficiário: Willian Fernando Zambuzzi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 16/08888-9 - Sinalização parácrina mediada por microvesículas e proteínas entre células ósseas e endoteliais durante o desenvolvimento e regeneração do tecido ósseo
• Beneficiário: Célio Junior da Costa Fernandes
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto