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Article

Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo

1
Division of Comprehensive Oral Health, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2
Oral and Craniofacial Health Sciences, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3
Cabrini University, Philadelphia, PA 19019, USA
4
Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5
Department of Bioengineering, Temple University, Philadelphia, PA 19122, USA
6
Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Antonella Forlino, Giacomina Brunetti and Pierre Moffatt
Int. J. Mol. Sci. 2021, 22(6), 3223; https://doi.org/10.3390/ijms22063223
Received: 9 February 2021 / Revised: 10 March 2021 / Accepted: 18 March 2021 / Published: 22 March 2021
(This article belongs to the Special Issue Osteoblast Differentiation and Activity in Skeletal Diseases)
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. View Full-Text
Keywords: collagen; bone; osteogenesis; hesperidin; extracellular matrix; regeneration; critical-sized defect; bone morphogenetic protein collagen; bone; osteogenesis; hesperidin; extracellular matrix; regeneration; critical-sized defect; bone morphogenetic protein
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MDPI and ACS Style

Miguez, P.A.; Tuin, S.A.; Robinson, A.G.; Belcher, J.; Jongwattanapisan, P.; Perley, K.; de Paiva Gonҫalves, V.; Hanifi, A.; Pleshko, N.; Barton, E.R. Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo. Int. J. Mol. Sci. 2021, 22, 3223. https://doi.org/10.3390/ijms22063223

AMA Style

Miguez PA, Tuin SA, Robinson AG, Belcher J, Jongwattanapisan P, Perley K, de Paiva Gonҫalves V, Hanifi A, Pleshko N, Barton ER. Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo. International Journal of Molecular Sciences. 2021; 22(6):3223. https://doi.org/10.3390/ijms22063223

Chicago/Turabian Style

Miguez, Patricia A., Stephen A. Tuin, Adam G. Robinson, Joyce Belcher, Prapaporn Jongwattanapisan, Kimberly Perley, Vinicius de Paiva Gonҫalves, Arash Hanifi, Nancy Pleshko, and Elisabeth R. Barton 2021. "Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo" International Journal of Molecular Sciences 22, no. 6: 3223. https://doi.org/10.3390/ijms22063223

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