title: The expression of collagen I and XII mRNAs in Porphyromonas gingivalis-induced periodontitis in rats: the effect of doxycycline and chemically modified tetracycline.
abstract: Tissue remodeling is a dynamic state in which a balance is achieved between the proteolytic breakdown and synthesis of the extracellular matrix. Type I collagen is a major component of the gingival connective tissue (GCT) and the periodontal ligament (PDL) throughout development, while type XII collagen has been found in the mature forms of these tissues. The purpose of this study was to investigate the effects of periodontitis on the expression of type I and XII collagen and subsequently to investigate the effects of doxycycline (DOXY) and chemically modified non-antimicrobial tetracycline (CMT-1) on the expression of these molecules in this model. Adult barrier-raised male Sprague-Dawley rats were inoculated with Porphyromonas gingivalis obtained from humans to create the experimental periodontitis. The animals with the P. gingivalis-induced periodontitis were then split into the following groups: Group A served as infected untreated controls (PGI group); group B was treated with doxycycline (DOXY group); and group C was treated with chemically modified tetracycline-1 (CMT-1 group). Group D contained uninfected animals that served as uninfected controls (NIC group). The expression of type I and XII collagen mRNAs was examined by in situ hybridization in each group, with the co-expression of these molecules representing mature and functional gingival connective tissue. In the NIC group, cells hybridized with digoxygenine-labeled cDNA probes encoding rat alpha2(I) or alpha1(XII) collagens were found distributed uniformly throughout the periodontal connective tissue. The PGI group showed little hybridization in the areas of infection, while both the DOXY and CMT-1 groups showed co-expression of the alpha2(I) and alpha1(XII) probes in the GCT and coronal part of the PDL. This study demonstrates that doxycycline and CMT-1 moderate or reduce the inhibitory effects of periodontal infection on the expression of type I and type XII collagen mRNAs. These results suggest that doxycycline and a form of non-antimicrobial tetracycline, chemically modified tetracycline-1, can reduce periodontal destruction by reversing the inhibitory effect of periodontal infection on collagen synthesis.
authors.affiliation: Laboratory of Reconstructive Biotechnology, Harvard School of Dental Medicine, Boston, MA 02115, USA. nkarimbu@warren.med.harvard.edu
authors.forename: N Y
authors.initials: NY
authors.lastname: Karimbux
authors.forename: N S
authors.initials: NS
authors.lastname: Ramamurthy
authors.forename: L M
authors.initials: LM
authors.lastname: Golub
authors.forename: I
authors.initials: I
authors.lastname: Nishimura
mesh_terms: D000345:Affinity Labels; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016866:Bacteroidaceae Infections; D003094:Collagen / Q000032:analysis / Q000187:drug effects / Q000235:genetics*; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism; D015342:DNA Probes; D018076:DNA, Complementary; D004076:Digoxigenin; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D010513:Periodontal Ligament / Q000187:drug effects / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism / Q000382:microbiology*; D016966:Porphyromonas gingivalis / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013752:Tetracycline / Q000494:pharmacology*
chemical_list: D000345:Affinity Labels; D000900:Anti-Bacterial Agents; D015342:DNA Probes; D018076:DNA, Complementary; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D012333:RNA, Messenger; C053450:4-des-dimethylaminotetracycline; D003094:Collagen; D013752:Tetracycline; D004318:Doxycycline; D004076:Digoxigenin