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We previously demonstrated that subantimicrobial-dose-doxycycline (SDD) treatment of post-menopausal osteopenic women significantly reduced periodontal disease progression, and biomarkers of collagen destruction and bone resorption locally in periodontal pockets, in a double-blind placebo-controlled clinical trial. We now hypothesize that SDD may also improve biomarkers of bone loss systemically in the same women, consistent with previous studies on tetracyclines (e.g., doxycycline) in organ culture and animal models of bone-deficiency disease. 128 post-menopausal osteopenic women with chronic periodontitis randomly received SDD or placebo tablets daily for 2 years adjunctive to periodontal maintenance therapy every 3-4 months. Blood was collected at baseline and at one- and two-year appointments, and sera were analyzed for bone resorption and bone formation/turnover biomarkers. In subsets of the study population, adjunctive SDD significantly reduced serum biomarkers of bone resorption (biomarkers of bone formation were unaffected), consistent with reduced risk of future systemic bone loss in these post-menopausal women not yet on anti-osteoporotic drugs. [ABSTRACT FROM AUTHOR]

We previously demonstrated that subantimicrobialdose- doxycycline (SDD) treatment of post-menopausal osteopenic women significantly reduced periodontal disease progression, and biomarkers of collagen destruction and bone resorption locally in periodontal pockets, in a double-blind placebo-controlled clinical trial. We now hypothesize that SDD may also improve biomarkers of bone loss systemically in the same women, consistent with previous studies on tetracyclines (e.g., doxycycline) in organ culture and animal models of bone-deficiency disease. 128 post-menopausal osteopenic women with chronic periodontitis randomly received SDD or placebo tablets daily for 2 years adjunctive to periodontal maintenance therapy every 3-4 months. Blood was collected at baseline and at one- and two-year appointments, and sera were analyzed for bone resorption and bone formation/turnover biomarkers. In subsets of the study population, adjunctive SDD significantly reduced serum biomarkers of bone resorption (biomarkers of bone formation were unaffected), consistent with reduced risk of future systemic bone loss in these post-menopausal women not yet on anti-osteoporotic drugs. [ABSTRACT FROM AUTHOR]

Orthodontic force induces biochemical responses in the periodontal ligament (PDL), but the matrix metalloproteinase (MMP)-dependent molecular mechanisms in orthodontically induced periodontal remodeling have remained unclear. Previous studies indicate that mechanical stress induces MMP-1 production in human PDL cells in vitro. We tested the hypothesis whether the in vivo levels, molecular forms, and degree of activation of MMP-1 and MMP-8 in gingival crevicular fluid (GCF) reflect an early stage of orthodontic tooth movement. Molecular forms of MMP-1 and MMP-8 were analyzed by Western blot, and MMP-8 levels by quantitative immunofluorometric assay (IFMA). The results showed that GCF MMP-8 levels for orthodontically treated teeth were significantly higher at 4-8 hrs after force application than before activation, and when compared with the control teeth (p < 0.05). Analysis of our data indicates that the cells within the periodontium are up-regulated to produce MMP-8, and the increased expression and activation of GCF MMP-8 reflect enhanced periodontal remodeling induced by orthodontic force. [ABSTRACT FROM AUTHOR]

MT1-MMP is a cell-membrane-bound metalloenzyme that activates other proMMPs such as proMMP-2 and -13. We studied MT1-MMP expression in mature human odontoblasts and pulp tissue, the regulation of MT1-MMP expression by growth factors TGF-β1 and BMP-2, and the activation of odontoblast-derived MMP-20 by MT1-MMP. MT1-MMP mRNA is expressed by native and cultured mature human odontoblasts and pulp tissue. Western blot analysis of human odontoblasts and pulp tissue detects 65- and 51-kDa pro- and active forms of MT1-MMP, and smaller truncated MT1-MMP forms. BMP-2 down-regulates MT1-MMP expression in odontoblasts and pulp tissue, while TGF-β1, alone or with BMP-2, decreases MT1-MMP mRNA levels only slightly. We also demonstrate that MT1-MMP is capable of converting proMMP-20 into a form corresponding to the active MMP-20. In conclusion, this study demonstrates the expression and differential regulation of MT1-MMP in human dentin-pulp complex cells, and the activation of MMP-20 by MT1-MMP. [ABSTRACT FROM AUTHOR]

Recent findings show that matrix metalloproteinase-8 (MMP-8) is expressed, in addition to neutrophils, by human chondrocytes, cultured fibroblasts, and endothelial cells. We investigated the expression of MMP-8 in other human mesenchyme-derived cells, odontoblasts, and pulp tissue. Odontoblasts and pulp tissue were collected from extracted human teeth for MMP-8 mRNA analysis with reverse-transcription/polymerase chain-reaction (RT-PCR) and Southern blot. The expression, localization, and secretion of MMP-8 protein were studied with Western blot, immunohistochemistry, and immunofluorometric assay. The effect of TGF-beta1 (10 ng/mL) on the expression, secretion, and concentration of secreted MMP-8 was studied by odontoblast and pulp tissue culture methods (Tjäderhane et al., 1998a). RT-PCR demonstrated MMP-8 mRNA expression in native and cultured odontoblasts and pulp tissue and cultured pulp fibroblasts, with a 522-bp transcript comparable with that of bone marrow cells. The specificity of PCR was confirmed with Southern blot. Western blot with MMP-8-specific antibody detected 65- and 50-kDa proteins in native samples, representing latent and active forms of mesenchymal-type MMP-8, and in the conditioned odontoblast culture media, 50-kDa protein was observed. TGF-beta down-regulated the MMP-8 mRNA and concentration of secreted protein in both cultures. Immunohistochemical staining detected MMP-8 in odontoblasts. These findings indicate that mesenchyme-derived cells of the dentin-pulp complex express, synthesize, and activate MMP-8, which may, in concert with odontoblast-derived gelatinases, participate in organization of dentin organic matrix prior to mineralization.