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Human Skin and Gingival Keratinocytes Show Differential Regulation of Matrix Metalloproteinases When Combined With Fibroblasts in 3‐Dimensional Cultures
Author(s) -
Chinnathambi Sathivel,
Bickenbach Jackie R.
Publication year - 2005
Publication title -
journal of periodontology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.036
H-Index - 156
eISSN - 1943-3670
pISSN - 0022-3492
DOI - 10.1902/jop.2005.76.7.1072
Subject(s) - matrix metalloproteinase , fibroblast , keratinocyte , chemistry , dermal fibroblast , matrix (chemical analysis) , human skin , microbiology and biotechnology , cell culture , biology , in vitro , biochemistry , chromatography , genetics
Background: Matrix metalloproteinases (MMP) and their inhibitors are expressed in tissues during interactions between keratinocytes and fibroblasts. Maintaining the balance between MMPs and their inhibitors is critical; failure to do so can lead to severe tissue damage or complete destruction, as seen in periodontal disease. Previously we showed that 3‐dimensional (3‐D) cultures of homotypically‐combined skin and gingival cells mimicked the tissues in protein and lipid production, but heterotypic cultures did not. Methods: We examined the production and activation of MMPs in these homotypic and heterotypic combinations of skin and gingival keratinocytes and fibroblasts during the critical time that they reformed the tissues. Primary fibroblasts and keratinocytes were isolated from normal human gingiva and skin and grown in 3‐D cultures for up to 42 days. MMP‐1, MMP‐2, and MMP‐9 in the media and inhibition of MMPs from these cultures were analyzed. Results: These experiments determined that skin fibroblasts grown with skin or gingival keratinocytes secrete increased amounts of MMP‐1 compared to gingival fibroblasts; that the interaction of keratinocytes with fibroblasts decreases the amount of MMP‐2 produced by the fibroblasts in 3‐D cultures; that skin keratinocytes, but not gingival keratinocytes, interact with fibroblasts to upregulate expression of the active form of MMP‐9; and that medium conditioned by gingival 3‐D cultures does not contain an inhibitor of MMP‐9 Conclusion: Varying the type of fibroblast beneath the keratinocytes allowed us to determine that skin and gingival keratinocytes differentially regulate the production and activation of MMP‐9, but not MMP‐2, a finding that could influence the success of tissue grafting after periodontal surgery. J Periodontol 2005;76:1072‐1083 .