Matrix metalloproteinases, tissue inhibitor of matrix metalloproteinase-1, and laminin-5 gamma 2 chain immunolocalization in gingival tissue of endotoxin-induced periodontitis in rats: Effects of low-dose doxycycline and alendronate
Küçük Resim Yok
Tarih
2007
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Amer Acad Periodontology
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background: Matrix metalloproteinases (MMPs) play important roles in tissue destruction mechanisms of periodontitis. MMP-8 and -13 are the major collagenases that act in extracellular matrix degradation in periodontal tissues. MMP-14 is a membrane-type MMP, and laminin (Ln)-5 is a basal membrane component. The aim of the present study was to evaluate the effects of doxycycline and alendronate on gingival tissue expression of MMP-8, -13, and -14; tissue inhibitors of MMP (TIMP)-1; and Ln-5 gamma 2 chain in experimental periodontitis induced by Escherichia coli endotoxin (LPS) in rats. Methods: Experimental periodontitis was induced by repeated injection of LPS. Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, LPS + doxycycline, LPS + alendronate, and LPS + doxycycline + alendronate. Doxycycline and alendronate were given as a single agent or as combination therapy during the 7 days of the experimental study period. On day 7, the rats were sacrificed, and the gingival tissues were analyzed immunohistochemically for expression of MMP-8, -13, and -14, Ln-5 gamma 2 chain, and TIMP-1. Alveolar bone loss was evaluated morphometrically under a stereomicroscope. Data were tested statistically by Kruskal-Wallis and Mann-Whitney tests and Spearman correlation analysis. Results: Alveolar bone loss was significantly higher in the LPS, doxycycline, alendronate, and combination groups than in the saline control group (all P < 0.01). MMP-8 expression was significantly higher in the LPS group than in the saline control group (P = 0.001). Individual administration of doxycycline or alendronate significantly decreased the expression of MMP-8 compared to LPS (P = 0.01). Combined drug administration reduced MMP-14 significantly compared to doxycycline (P = 0.004). No significant differences in Ln-5 gamma 2 chain expression were found between the study groups (P > 0.05). MMP-14 significantly correlated with the Ln-5 gamma 2 chain in the LPS + alendronate group (P = 0.04) and with the amount of alveolar bone loss in the LPS + doxycycline + alendronate group (P = 0.03). Conclusions: Our findings suggest that alendronate and/or doxycycline may inhibit MMP-8 expression significantly; particularly, their combined administration may provide beneficial effects in periodontal treatment. Moreover, individual administration of alendronate and doxycycline results in significant increases in TIMP-I expression in gingiva. However, these effects of combined low-dose doxycycline and alendronate on MMPs and TIMP should be verified by clinical human trials before these agents are used in dental practice.
Açıklama
Anahtar Kelimeler
alendronate, bisphosphonates, doxycycline, laminin 5, MMPs, TIMP-1
Kaynak
Journal of Periodontology
WoS Q Değeri
Q1
Scopus Q Değeri
Cilt
78
Sayı
1