Modulatory effects of silibinin in cell behavior during osteogenic phenotype

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Journal of Cellular Biochemistry; v. 120, n. 8, p. 13413-13425, AUG 2019.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 14/22689-3 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
• Grantee: Willian Fernando Zambuzzi
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/08888-9 - Microvesicle/proteins-mediated paracrine signaling among bone and endothelial cells during bone development and regeneration
• Grantee: Célio Junior da Costa Fernandes
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)