Modulatory effects of silibinin in cell behavior during osteogenic phenotype

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 μg/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 foldchanges), 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 conju nction, 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. K E Y W O R D S bone, flavonoid, inflammation, osteoblast, remodeling, silibinin

Biomineralization inspired 3D printed bioactive glass nanocomposite scaffolds orchestrate diabetic bone regeneration by remodeling micromilieu

“…Sr 2+ could promote the adhesion and proliferation of cells on biomaterials [ 60 ]. Cytoskeleton rearrangement is required to drive morphological changes in cells during adhesion and differentiation processes, as well as to guide the release of calcification vesicles into the ECM [ 61 ]. Importantly, Src has also been related to governing ECM remodeling by somehow contributing to matrix metalloproteinase (MMP) involvement in response to biomaterials.…”

Silymarin and Inflammation: Food for Thoughts

“…In human chondrocytes in vitro, SB was demonstrated to inhibit the expression of IL-1β-induced inflammatory markers, including COX-2, iNOS, NF-κB, NO, PGE2, TNF-α and IL-6 [68]. Similarly, SB (0.42 mM) regulated intracellular signalling to reprogram the inflammatory response in osteoblast SB [69]. In summary, SB was shown to be protective against osteoarthritis (OA) through inhibiting the inflammatory response and cartilage matrix degradation in vitro (in human OA chondrocytes) and in vivo (in mice OA models).…”

Natural anti‐inflammatory products for osteoarthritis: From molecular mechanism to drug delivery systems and clinical trials

“…In addition, either the effect or mechanism of silybin or silibinin on OA subchondral bone destruction has not been fully explored. However, studies on different osteoblasts reported that the active component of silymarin, silybin, has effects on adhesion, proliferation, and differentiation processes of mice osteoblast (Fernandes et al, 2019), another study reported that silybin increases the mRNA expression of COL‐1, ALP, OCN, BMP‐2, and RUNX2 thereby improving osteogenic differentiation of human BMSCs (Ying et al, 2013). Therefore, the effect of silymarin‐associated components on OA subchondral bone destruction is worthy of study.…”

“…Improves osteogenic differentiation of BMSCs (Fernandes et al, 2019;Ying et al, 2013) Abbreviations: ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; COX, cyclooxygenase; ECM, extracellular matrix; ER, endoplasmic reticulum; IL-1, interleukin-1; MDA, malondialdehyde; MMP, matrix metalloproteinase; NAIP, natural anti-inflammatory product; PARP, poly ADP-ribose polymerase; ROS, reactive oxygen species; TNF-α, tumor necrosis factor-α.…”