Polyphenols from Grape Pomace Induce Osteogenic Differentiation in Mesenchymal Stem Cells

Overview

Journal Int J Mol Med

Specialty Genetics

Date 2020 Apr 3

PMID 32236566

Citations 17

Authors

Elisa Torre

Giorgio Iviglia

Clara Cassinelli

Marco Morra

Nazario Russo

Affiliations

Soon will be listed here.

Abstract

Polyphenols are increasingly investigated for the treatment of periodontitis and research on their use in dental biomaterials is currently being conducted. Grape pomace extracts are a rich source of polyphenols. In the present study, the polyphenols of two different types of grape pomace were characterized and identified by high‑performance liquid chromatography‑diode array detector, and the effect of polyphenol‑rich grape pomace extracts on mesenchymal stem cell (MSC) osteogenic differentiation was investigated. Solid‑liquid extraction was used to recover polyphenols from red and white grape pomace. The two extracts have been characterized through the phenolic content and antioxidant power. Human MSCs (hMSCs) from the bone marrow were cultured both with and without given amounts (10 or 20 µg/ml) of the obtained pomace extracts. Their effects on cell differentiation were evaluated by reverse transcription‑quantitative polymerase chain reaction, compared with relevant controls. Results showed that both pomace extracts, albeit different in phenolic composition and concentration, induced multiple effects on hMSC gene expression, such as a decreased receptor activator of nuclear factor κ‑Β ligand/osteoprotegerin ratio and an enhanced expression of genes involved in osteoblast differentiation, thus suggesting a shift of hMSCs towards osteoblast differentiation. The obtained results provided data in favor of the exploitation of polyphenol properties from grape pomace extracts as complementary active molecules for dental materials and devices for bone regeneration in periodontal defects.

Citing Articles

Nutrients and Nutraceuticals from L. Pomace: Biological Activities, Valorization, and Potential Applications.

Prata C, Zalambani C, Rossi F, Rossello S, Cerchiara T, Cappadone C Nutrients. 2025; 17(3).

PMID: 39940441 PMC: 11820150. DOI: 10.3390/nu17030583.

Polyphenolic Screening and the Antioxidant Activity of Grape Pomace Extracts of Romanian White and Red Grape Varieties.

Radulescu C, Olteanu R, Buruleanu C, Tudorache M, Dulama I, Stirbescu R Antioxidants (Basel). 2024; 13(9).

PMID: 39334792 PMC: 11429185. DOI: 10.3390/antiox13091133.

Preliminary Evaluation of Bioactive Collagen-Polyphenol Surface Nanolayers on Titanium Implants: An X-ray Photoelectron Spectroscopy and Bone Implant Study.

Morra M, Iviglia G, Cassinelli C, Sartori M, Cavazza L, Martini L J Funct Biomater. 2024; 15(7).

PMID: 39057292 PMC: 11278435. DOI: 10.3390/jfb15070170.

Bifunctional mesoporous glasses for bone tissue engineering: Biological effects of doping with cerium and polyphenols in 2D and 3D in vitro models.

Menshikh K, Reddy A, Cochis A, Fraulini F, Zambon A, Lusvardi G Biomater Biosyst. 2024; 14:100095.

PMID: 38912165 PMC: 11192985. DOI: 10.1016/j.bbiosy.2024.100095.

Polyphenols in Oral Health: Homeostasis Maintenance, Disease Prevention, and Therapeutic Applications.

Guo Y, Li Z, Chen F, Chai Y Nutrients. 2023; 15(20).

PMID: 37892459 PMC: 10610286. DOI: 10.3390/nu15204384.

References

Sheu S, Tsai C, Sun J, Chen M, Liu M, Sun M . Stimulatory effect of puerarin on bone formation through co-activation of nitric oxide and bone morphogenetic protein-2/mitogen-activated protein kinases pathways in mice. Chin Med J (Engl). 2012; 125(20):3646-53. View

Torre E . Molecular signaling mechanisms behind polyphenol-induced bone anabolism. Phytochem Rev. 2017; 16(6):1183-1226. PMC: 5696504. DOI: 10.1007/s11101-017-9529-x. View

Abdel-Naim A, Alghamdi A, Algandaby M, Al-Abbasi F, Al-Abd A, Eid B . Rutin Isolated from Enhances Bone Cell Proliferation and Ossification Markers. Oxid Med Cell Longev. 2018; 2018:5106469. PMC: 5831974. DOI: 10.1155/2018/5106469. View

Bu S, Hunt T, Smith B . Dried plum polyphenols attenuate the detrimental effects of TNF-alpha on osteoblast function coincident with up-regulation of Runx2, Osterix and IGF-I. J Nutr Biochem. 2008; 20(1):35-44. DOI: 10.1016/j.jnutbio.2007.11.012. View

Gomez-Florit M, Pacha-Olivenza M, Fernandez-Calderon M, Cordoba A, Gonzalez-Martin M, Monjo M . Quercitrin-nanocoated titanium surfaces favour gingival cells against oral bacteria. Sci Rep. 2016; 6:22444. PMC: 4772538. DOI: 10.1038/srep22444. View

Dai Z, Li Y, Quarles L, Song T, Pan W, Zhou H . Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine. 2007; 14(12):806-14. DOI: 10.1016/j.phymed.2007.04.003. View

Gao J, Feng Z, Wang X, Zeng M, Liu J, Han S . SIRT3/SOD2 maintains osteoblast differentiation and bone formation by regulating mitochondrial stress. Cell Death Differ. 2017; 25(2):229-240. PMC: 5762839. DOI: 10.1038/cdd.2017.144. View

Palaska I, Papathanasiou E, Theoharides T . Use of polyphenols in periodontal inflammation. Eur J Pharmacol. 2013; 720(1-3):77-83. DOI: 10.1016/j.ejphar.2013.10.047. View

Yang L, Takai H, Utsunomiya T, Li X, Li Z, Wang Z . Kaempferol stimulates bone sialoprotein gene transcription and new bone formation. J Cell Biochem. 2010; 110(6):1342-55. DOI: 10.1002/jcb.22649. View

10.

Tominari T, Hirata M, Matsumoto C, Inada M, Miyaura C . Polymethoxy flavonoids, nobiletin and tangeretin, prevent lipopolysaccharide-induced inflammatory bone loss in an experimental model for periodontitis. J Pharmacol Sci. 2012; 119(4):390-4. DOI: 10.1254/jphs.11188sc. View

11.

Shen C, Wang P, Guerrieri J, Yeh J, Wang J . Protective effect of green tea polyphenols on bone loss in middle-aged female rats. Osteoporos Int. 2007; 19(7):979-90. DOI: 10.1007/s00198-007-0527-5. View

12.

Lazar L, Loghin A, Bud E, Cerghizan D, Horvath E, Nagy E . Cyclooxygenase-2 and matrix metalloproteinase-9 expressions correlate with tissue inflammation degree in periodontal disease. Rom J Morphol Embryol. 2016; 56(4):1441-6. View

13.

Rothwell J, Perez-Jimenez J, Neveu V, Medina-Remon A, Mhiri N, Garcia-Lobato P . Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content. Database (Oxford). 2013; 2013:bat070. PMC: 3792339. DOI: 10.1093/database/bat070. View

14.

Neveu V, Perez-Jimenez J, Vos F, Crespy V, du Chaffaut L, Mennen L . Phenol-Explorer: an online comprehensive database on polyphenol contents in foods. Database (Oxford). 2010; 2010:bap024. PMC: 2860900. DOI: 10.1093/database/bap024. View

15.

Lin S, Kang L, Wang C, Huang H, Cheng T, Huang H . (-)-Epigallocatechin-3-Gallate (EGCG) Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells. Molecules. 2018; 23(12). PMC: 6321548. DOI: 10.3390/molecules23123221. View

16.

Jung W . Protective effect of apigenin against oxidative stress-induced damage in osteoblastic cells. Int J Mol Med. 2014; 33(5):1327-34. DOI: 10.3892/ijmm.2014.1666. View

17.

Bunte K, Hensel A, Beikler T . Polyphenols in the prevention and treatment of periodontal disease: A systematic review of in vivo, ex vivo and in vitro studies. Fitoterapia. 2018; 132:30-39. DOI: 10.1016/j.fitote.2018.11.012. View

18.

Arumugam B, Balagangadharan K, Selvamurugan N . Syringic acid, a phenolic acid, promotes osteoblast differentiation by stimulation of Runx2 expression and targeting of Smad7 by miR-21 in mouse mesenchymal stem cells. J Cell Commun Signal. 2018; 12(3):561-573. PMC: 6039342. DOI: 10.1007/s12079-018-0449-3. View

19.

Austermann K, Baecker N, Stehle P, Heer M . Putative Effects of Nutritive Polyphenols on Bone Metabolism In Vivo-Evidence from Human Studies. Nutrients. 2019; 11(4). PMC: 6520874. DOI: 10.3390/nu11040871. View

20.

Huang J, Bao Y, Xiang W, Jing X, Guo J, Yao X . Icariin Regulates the Bidirectional Differentiation of Bone Marrow Mesenchymal Stem Cells through Canonical Wnt Signaling Pathway. Evid Based Complement Alternat Med. 2018; 2017:8085325. PMC: 5763109. DOI: 10.1155/2017/8085325. View