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Article ; Online: Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo.

Miguez, Patricia A / Tuin, Stephen A / Robinson, Adam G / Belcher, Joyce / Jongwattanapisan, Prapaporn / Perley, Kimberly / de Paiva Gonҫalves, Vinicius / Hanifi, Arash / Pleshko, Nancy / Barton, Elisabeth R

International journal of molecular sciences

2021  Volume 22, Issue 6

Abstract: This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and ... ...

Abstract This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin's influence in mineralized tissue formation and regeneration. Hesperidin was added to a culture of MC3T3-E1 cells at various concentrations. Cell proliferation, viability, osteogenic gene expression and deposited collagen matrix analyses were performed. Treatment with hesperidin showed significant upregulation of osteogenic markers, particularly with lower doses. Mature and compact collagen fibrils in hesperidin-treated cultures were observed by picrosirius red staining (PSR), although a thinner matrix layer was present for the higher dose of hesperidin compared to osteogenic media alone. Fourier-transform infrared spectroscopy indicated a better mineral-to-matrix ratio and matrix distribution in cultures exposed to hesperidin and confirmed less collagen deposited with the 100-µM dose of hesperidin. In vivo, hesperidin combined with a suboptimal dose of bone morphogenetic protein 2 (BMP2) (dose unable to promote healing of a rat mandible critical-sized bone defect) in a collagenous scaffold promoted a well-controlled (not ectopic) pattern of bone formation as compared to a large dose of BMP2 (previously defined as optimal in healing the critical-sized defect, although of ectopic nature). PSR staining of newly formed bone demonstrated that hesperidin can promote maturation of bone organic matrix. Our findings show, for the first time, that hesperidin has a modulatory role in mineralized tissue formation via not only osteoblast cell differentiation but also matrix organization and matrix-to-mineral ratio and could be a potential adjunct in regenerative bone therapies.
MeSH term(s) Animals ; Bone Morphogenetic Protein 2/pharmacology ; Bone Regeneration ; Calcification, Physiologic/drug effects ; Cell Line ; Cells, Cultured ; Collagen/metabolism ; Extracellular Matrix/metabolism ; Hesperidin/pharmacology ; Mice ; Osteoblasts/drug effects ; Osteoblasts/metabolism ; Osteogenesis/drug effects ; Rats
Chemical Substances Bmp2 protein, mouse ; Bone Morphogenetic Protein 2 ; Collagen (9007-34-5) ; Hesperidin (E750O06Y6O)
Language English
Publishing date 2021-03-22
Publishing country Switzerland
Document type Journal Article
ZDB-ID 2019364-6
ISSN 1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online) 1422-0067
ISSN 1422-0067 ; 1661-6596
DOI 10.3390/ijms22063223
Database MEDical Literature Analysis and Retrieval System OnLINE

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