4.7 Article

Rutin-Zn(II) complex promotes bone formation-A concise assessment in human dental pulp stem cells and zebrafish

Journal

CHEMICO-BIOLOGICAL INTERACTIONS
Volume 349, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2021.109674

Keywords

MicroRNA-143-3p; HDAC7; Flavonoid metal complex; hDPSCs; Osteoblast differentiation; Zebrafish

Funding

  1. Department of Science and Technology, INSPIRE Faculty Program, Government of India [DST/INSPIRE/04/2017/002913]

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The study evaluated the molecular role of Rutin and rutin-Zn(II) complex on osteoblast differentiation and mineralization in human dental pulp cells and zebrafish model, finding them to be non-toxic and enhancing the expression of osteoblast differentiation marker genes and calcium deposition. The results suggest that Rutin-Zn(II) complex may serve as a novel agent for bone tissue engineering applications.
We have assessed the molecular role of Rutin and rutin-Zn(II) complex on osteoblast differentiation and mineralization in human dental pulp cells and zebrafish model. The biocompatibility of the rutin-Zn(II) complex was determined using MTT and chick embryotoxicity assays. Alizarin red staining and ALP measurements were performed to study the osteogenic role of Rutin and rutin-Zn(II) complex at the cellular level in hDPSCs. At molecular level, following rutin and rutin-Zn(II) exposure, the mRNA expression profile of osteoblast markers such Runx2, type 1 col, OC, and ON were investigated. In addition to this, the expression of negative regulators of osteoblast development such Smad7, Smurf1, and HDAC7 waere studied by Real time RT-PCR analysis. The osteogenic role of prepared complex under in vivo was studied by an in-house zebrafish scale model followed by osteoblast differentiation markers expression profiling and Ca:P level measurement by ICP-MS. Rutin and the rutin-Zn(II) complex were found to be non-toxic till 10 mu M and increased the expression of osteoblast differentiation marker genes. It also enhanced calcium deposition in both in vitro and in vivo models. Osteogenic property of rutin-Zn(II) in hDPSCs was found be mediated by Smad7, Smurf1, and HDAC7 and enhancing Runx2 expression. Our study warrants the possible use of rutin-Zn(II) as nave agent or in combination with other bone scaffolding systems/materials for bone tissue engineering applications.

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