Activity of two hyaluronan preparations on primary human oral fibroblasts.
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cells, Cultured
Collagen Type III
/ genetics
Connective Tissue
/ physiology
Drug Compounding
Fibroblasts
/ drug effects
Gene Expression
/ drug effects
Gingiva
/ cytology
Humans
Hyaluronic Acid
/ administration & dosage
Matrix Metalloproteinase 2
/ genetics
Matrix Metalloproteinase 3
/ genetics
Palate
/ cytology
Regeneration
/ drug effects
Regenerative Endodontics
Transforming Growth Factor beta3
/ genetics
Wound Healing
/ drug effects
gene expression
growth factors
hyaluronic acid
oral soft tissue wound healing
pro-inflammatory cytokines
Journal
Journal of periodontal research
ISSN: 1600-0765
Titre abrégé: J Periodontal Res
Pays: United States
ID NLM: 0055107
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
03
05
2018
revised:
20
07
2018
accepted:
02
08
2018
pubmed:
29
9
2018
medline:
14
5
2019
entrez:
29
9
2018
Statut:
ppublish
Résumé
The potential benefit of using hyaluronan (HA) in reconstructive periodontal surgery is still a matter of debate. The aim of the present study was to evaluate the effects of two HA formulations on human oral fibroblasts involved in soft tissue wound healing/regeneration. Metabolic, proliferative and migratory abilities of primary human palatal and gingival fibroblasts were examined upon HA treatment. To uncover the mechanisms whereby HA influences cellular behavior, wound healing-related gene expression and activation of signaling kinases were analyzed by qRT-PCR and immunoblotting, respectively. The investigated HA formulations maintained the viability of oral fibroblasts and increased their proliferative and migratory abilities. They enhanced expression of genes encoding type III collagen and transforming growth factor-β3, characteristic of scarless wound healing. The HAs upregulated the expression of genes encoding pro-proliferative, pro-migratory, and pro-inflammatory factors, with only a moderate effect on the latter in gingival fibroblasts. In palatal but not gingival fibroblasts, an indirect effect of HA on the expression of matrix metalloproteinases 2 and 3 was detected, potentially exerted through induction of pro-inflammatory cytokines. Finally, our data pointed on Akt, Erk1/2 and p38 as the signaling molecules whereby the HAs exert their effects on oral fibroblasts. Both investigated HA formulations are biocompatible and enhance the proliferative, migratory and wound healing properties of cell types involved in soft tissue wound healing following regenerative periodontal surgery. Our data further suggest that in gingival tissues, the HAs are not likely to impair the healing process by prolonging inflammation or causing excessive MMP expression at the repair site.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
The potential benefit of using hyaluronan (HA) in reconstructive periodontal surgery is still a matter of debate. The aim of the present study was to evaluate the effects of two HA formulations on human oral fibroblasts involved in soft tissue wound healing/regeneration.
MATERIAL AND METHODS
METHODS
Metabolic, proliferative and migratory abilities of primary human palatal and gingival fibroblasts were examined upon HA treatment. To uncover the mechanisms whereby HA influences cellular behavior, wound healing-related gene expression and activation of signaling kinases were analyzed by qRT-PCR and immunoblotting, respectively.
RESULTS
RESULTS
The investigated HA formulations maintained the viability of oral fibroblasts and increased their proliferative and migratory abilities. They enhanced expression of genes encoding type III collagen and transforming growth factor-β3, characteristic of scarless wound healing. The HAs upregulated the expression of genes encoding pro-proliferative, pro-migratory, and pro-inflammatory factors, with only a moderate effect on the latter in gingival fibroblasts. In palatal but not gingival fibroblasts, an indirect effect of HA on the expression of matrix metalloproteinases 2 and 3 was detected, potentially exerted through induction of pro-inflammatory cytokines. Finally, our data pointed on Akt, Erk1/2 and p38 as the signaling molecules whereby the HAs exert their effects on oral fibroblasts.
CONCLUSION
CONCLUSIONS
Both investigated HA formulations are biocompatible and enhance the proliferative, migratory and wound healing properties of cell types involved in soft tissue wound healing following regenerative periodontal surgery. Our data further suggest that in gingival tissues, the HAs are not likely to impair the healing process by prolonging inflammation or causing excessive MMP expression at the repair site.
Identifiants
pubmed: 30264516
doi: 10.1111/jre.12602
pmc: PMC6586051
doi:
Substances chimiques
Collagen Type III
0
Transforming Growth Factor beta3
0
Hyaluronic Acid
9004-61-9
Matrix Metalloproteinase 3
EC 3.4.24.17
Matrix Metalloproteinase 2
EC 3.4.24.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
33-45Subventions
Organisme : Regedent, Zürich, Switzerland
Informations de copyright
© 2018 The Authors. Journal of Periodontal Research Published by John Wiley & Sons Ltd.
Références
Biochem Med Metab Biol. 1986 Apr;35(2):219-26
pubmed: 3707753
J Biol Chem. 1998 May 1;273(18):11342-8
pubmed: 9556628
Int J Med Sci. 2009;6(2):65-71
pubmed: 19277251
J Biol Chem. 1986 Mar 25;261(9):4337-45
pubmed: 3456347
Arh Hig Rada Toksikol. 2011 Jun;62(2):155-61
pubmed: 21705303
Lab Invest. 1994 Feb;70(2):176-82
pubmed: 8139259
J Biomed Mater Res A. 2003 Sep 15;66(4):880-4
pubmed: 12926041
Ann Surg. 1991 Apr;213(4):292-6
pubmed: 2009010
Rheumatology (Oxford). 2009 Jan;48(1):45-8
pubmed: 19056796
Int J Rheum Dis. 2016 Jun;19(6):557-66
pubmed: 25291965
Biochem Biophys Res Commun. 2015 Sep 25;465(3):569-74
pubmed: 26284973
J Periodontol. 2002 Nov;73(11):1331-7
pubmed: 12479638
J Exp Med. 1985 Dec 1;162(6):2163-8
pubmed: 2999289
J Oral Sci. 2003 Jun;45(2):85-91
pubmed: 12930131
Arch Oral Biol. 1989;34(7):587-9
pubmed: 2512903
Clin Oral Investig. 2019 Mar;23(3):1133-1141
pubmed: 29961138
Wound Repair Regen. 2009 Mar-Apr;17(2):153-62
pubmed: 19320882
J Biomed Mater Res. 1995 Jul;29(7):829-34
pubmed: 7593021
J Periodontal Res. 2019 Feb;54(1):33-45
pubmed: 30264516
J Clin Periodontol. 2015 Mar;42(3):236-46
pubmed: 25640222
Matrix Biol. 2002 Jan;21(1):25-9
pubmed: 11827789
Osteoarthritis Cartilage. 2006 Dec;14(12):1237-47
pubmed: 16806998
J Oral Pathol Med. 2003 Jul;32(6):358-66
pubmed: 12787043
FASEB J. 2011 Oct;25(10):3477-88
pubmed: 21705668
J Biol Chem. 2001 Jun 8;276(23):20428-35
pubmed: 11262389
J Gastroenterol. 2004;39(4):346-54
pubmed: 15168246
Eur Rev Med Pharmacol Sci. 2014;18(21):3326-38
pubmed: 25487947
Int J Biochem Cell Biol. 2008;40(6-7):1334-47
pubmed: 18083622
J Dent Res. 1989 Jan;68(1):20-5
pubmed: 2910955
J Biol Chem. 2002 Feb 15;277(7):4589-92
pubmed: 11717317
J Pharm Pharm Sci. 2015;18(1):53-60
pubmed: 25877441
Biochim Biophys Acta. 1990 Apr 23;1034(1):39-45
pubmed: 2328260
J Periodontol. 2001 Mar;72(3):331-40
pubmed: 11327060
J Periodontal Res. 1988 Jan;23(1):13-7
pubmed: 2963899
J Biomed Mater Res A. 2016 Jun;104(6):1560-9
pubmed: 27007721
Wound Repair Regen. 2005 Mar-Apr;13(2):198-204
pubmed: 15828945
Biochem J. 2007 Jun 1;404(2):327-36
pubmed: 17324121
Wound Repair Regen. 2008 Mar-Apr;16(2):274-87
pubmed: 18282267
Cell Tissue Res. 1998 Nov;294(2):323-33
pubmed: 9799448
Periodontol 2000. 2000 Oct;24:193-214
pubmed: 11276867
J Endod. 2006 Mar;32(3):186-92
pubmed: 16500223
Clin Exp Dermatol. 2008 Mar;33(2):176-82
pubmed: 18257838
Am J Physiol. 1997 Oct;273(4):C1151-9
pubmed: 9357758
Connect Tissue Res. 1981;9(2):99-106
pubmed: 6458453
Biochem Res Int. 2012;2012:875742
pubmed: 22500233
Int J Oral Sci. 2018 Jun 12;10(2):20
pubmed: 29895828
J Indian Soc Periodontol. 2016 Jan-Feb;20(1):50-6
pubmed: 27041838
Arch Oral Biol. 1982;27(2):177-9
pubmed: 6805449
PLoS One. 2008 Apr 02;3(4):e1886
pubmed: 18382669
J Endod. 2006 Sep;32(9):853-61
pubmed: 16934628
J Indian Soc Periodontol. 2014 Nov-Dec;18(6):746-50
pubmed: 25624632
Front Immunol. 2015 Jun 02;6:261
pubmed: 26082778
Exp Dermatol. 2010 Aug;19(8):e336-9
pubmed: 20500771
Mol Cancer. 2014 Feb 05;13:22
pubmed: 24495796
Burns. 2003 Sep;29(6):527-31
pubmed: 12927975
Mol Biol Cell. 2001 Jun;12(6):1859-68
pubmed: 11408591
J Periodontal Res. 1997 Nov;32(8):634-45
pubmed: 9409458
J Biol Chem. 2011 May 20;286(20):17618-30
pubmed: 21454519
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
J Biol Chem. 2006 Jun 30;281(26):17952-60
pubmed: 16648633
Wound Repair Regen. 2016 Mar;24(2):215-22
pubmed: 26704519
J Periodontal Res. 2005 Jun;40(3):245-51
pubmed: 15853971
J Biol Chem. 2002 Oct 25;277(43):41046-59
pubmed: 12194965
Physiol Rev. 2003 Jul;83(3):835-70
pubmed: 12843410