title: Matrix metalloproteinase-8 regulates transforming growth factor-β1 levels in mouse tongue wounds and fibroblasts in vitro.
abstract: Matrix metalloproteinase-8 (MMP-8)-deficient mice (Mmp8-/-) exhibit delayed dermal wound healing, but also partly contradicting results have been reported. Using the Mmp8-/- mice we investigated the role of MMP-8 in acute wound healing of the mobile tongue, and analyzed the function of tongue fibroblasts in vitro. Interestingly, in the early phase the tongue wounds of Mmp8-/- mice healed faster than those of wild type (wt) mice resulting in significant difference in wound widths (P=0.001, 6-24h). The Mmp8-/- wounds showed no change in myeloperoxidase positive myeloid cell count, but the level of transforming growth factor (TGF)-β1 was significantly increased (P=0.007) compared to the wt tongues. Fibroblasts cultured from wt tongues expressed MMP-8 and TGF-β1. However, higher TGF-β1 levels were detected in Mmp8-/- fibroblasts, and MMP-8 treatment decreased phosphorylated Smad-2 levels and α-smooth muscle actin expression in these fibroblasts suggesting reduced TGF-β1 signaling. Consistently, a degradation of recombinant TGF-β1 by MMP-8 decreased its ability to activate the signaling cascade in fibroblasts. Moreover, collagen gels with Mmp8-/- fibroblasts reduced more in size. We conclude that MMP-8 regulates tongue wound contraction rate and TGF-β1 levels. In vitro analyses suggest that MMP-8 may also play a role in regulating TGF-β1 signaling of stromal fibroblasts.
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, PO Box 5281, Oulu 90014, Finland; Medical Research Center (MRC), Oulu, Finland. Electronic address: pirjo.astrom@oulu.fi.
authors.forename: Pirjo
authors.initials: P
authors.lastname: Åström
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, PO Box 5281, Oulu 90014, Finland; Medical Research Center (MRC), Oulu, Finland. Electronic address: emma.pirila@oulu.fi.
authors.forename: Emma
authors.initials: E
authors.lastname: Pirilä
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, PO Box 5281, Oulu 90014, Finland. Electronic address: riitta.lithovius@gmail.com.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lithovius
authors.affiliation: Department of Oral and Maxillofacial Diseases, Institute of Dentistry, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland. Electronic address: heidi.holappa@helsinki.fi.
authors.forename: Heidi
authors.initials: H
authors.lastname: Heikkola
authors.affiliation: Department of Oral and Maxillofacial Surgery, Institute of Dentistry, University of Oulu, Oulu University Hospital, Oulu, Finland. Electronic address: jarkko.korpi@helsinki.fi.
authors.forename: Jarkko T
authors.initials: JT
authors.lastname: Korpi
authors.affiliation: Department of Pathology and Laboratory of Periodontal Biology, Faculty of Dentistry, University of Chile, Santiago, Chile. Electronic address: mhernandezrios@gmail.com.
authors.forename: Marcela
authors.initials: M
authors.lastname: Hernández
authors.affiliation: Department of Oral and Maxillofacial Diseases, Institute of Dentistry, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland; Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden. Electronic address: timo.sorsa@helsinki.fi.
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.affiliation: Department of Diagnostics and Oral Medicine, Institute of Dentistry, University of Oulu, PO Box 5281, Oulu 90014, Finland; Oulu University Hospital, Oulu, Finland, Institute of Dentistry, University of Helsinki, Helsinki, Finland; Graduate Program in Estomatopatologia, Piracicaba Dental School, University of Campinas, Piracicaba-São Paulo, Brazil; Medical Research Center (MRC), Oulu, Finland. Electronic address: tuula.salo@oulu.fi.
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012867:Skin / Q000293:injuries / Q000378:metabolism*; D014059:Tongue / Q000293:injuries / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C576328:MMP8 protein, mouse; D020784:Matrix Metalloproteinase 8
keywords: Fibroblasts; Matrix metalloproteinase-8; Mouse; Transforming growth factor beta1