The regulation of lysyl oxidase by bFGF and TGF-B1 in osteoblastic MC3T3-E1 Cells

Thesis (D.Sc.D.)--Boston University, Henry M. Goldman School of Graduate Dentistry, 1995 (Oral Biology).Includes bibliographical references: (leaves 57-73).Lysyl oxidase catalyzes the enzymatic step that is limiting for collagen and elastin crosslinking. As a crosslinked collagenous extracellular matrix is required for bone formation, mineralization and structural integrity, regulation of lysyl oxidase in osteoblastic cells, although not previously studied, is likely to have relevance to bone synthesis and repair. The goals of this study were to determine whether lysyl oxidase, like its type I collagen substrate, is regulated by basic fibroblast growth factor (bFGF) and transforming growth factor beta-1(TGF-[beta] 1) in osteoblastic MC3T3-E1 cells. We also established the degree of posttranscriptional control by bFGF. Steady-state lysyl oxidase mRNA levels were decreased to 30% of control after 24 hours of treatment with 1 nM and 10 nM bFGF. This regulation was time-dependent. Similarly, the COL1A1 mRNA level decreased to less than 10% of control after 24 hours of treatment. Media lysyl oxidase activity decreased in accordance with the steady-state mRNA changes in bFGF-treated cultures that were refed after 24 hours of growth factor treatment. Treatment of MC3T3-E1 cells with 0.01 – 0.1 nM bFGF for 24 hours, and treatment with 1 nM bFGF for up to 12 hours resulted in a modest stimulation of lysyl oxidase gene expression and enzyme activity. Fifty per cent of the down-regulation of lysyl oxidase was shown to be posttranscriptional by measuring bFGF-dependent-differences in decay rates of lysyl oxidase mRNA in the presence of 5,6-dichloro- 1 [Beta] D-ribofuranoaylbenzimidazole. New protein synthesis was not required for the down-regulation by bFGF, but cycloheximide did increase constitutive lysyl oxidase mRNA levels 2.5-fold. GAPDH or COL1A1 mRNA levels were not affected by cycloheximide. TGF-[Beta] 1 increased the levels of steady-state lysyl oxidase mRNA, proenzyme synthesis and secretion, and enzyme activity in a dose- and time-dependent manner. A discrepancy between the synthesis of lysyl oxidase proenzyme and enzyme activity indicated that the posttranstational maturation of lysyl oxidase may limit full activation of lysyl oxidase enzyme activity. TGF-[Beta] 1-mediated effects on steady-state lysyl oxidase mRNA levels are greater than th e effects on steady-state COL1A1 mRNA levels, suggesting that lysyl oxidase is a major target for TGF-[Beta]1 in this cell culture model. Mechanisms of regulation of lysyl oxidase and the possible role of lysyl oxidase activity in controlling collagen accuImulation in mineralized tissues are discussed

The effects of sodium alendronate on socket healing after tooth extraction: a systematic review of animal studies

Abstract The aim of this systematic review was to answer the following question: “Does alendronate, a nitrogen-containing bisphosphonate, improve or impair alveolar socket healing after tooth extraction in animal models”? To this end, a systematic review of the literature was carried out in PubMed, Scopus, LILACS, Web of Science, as well as in the gray literature up to May 2023. Preclinical studies that evaluated alveolar healing after tooth extraction and the intake of sodium alendronate compared with placebo were included. Two investigators were responsible for screening the articles independently, extracting the data, and assessing their quality through the SYRCLE’s RoB tool for randomized trials in animal studies. The study selection process, study characteristics, risk of bias in studies, impact of alendronate on bone healing, and certainty of evidence were described in text and table formats. Methodological differences among the studies were restricted to the synthesis methods. The synthesis of qualitative results followed the Synthesis Without Meta-analysis (SWiM) reporting guideline. From the 19 included studies, five were considered to have low risk, three were of unclear risk, and eleven presented a high risk of bias. The studies were considered heterogeneous regarding alendronate posology, including its dosage and route of administration. Furthermore, a variety of animal species, different age ranges, diverse teeth extracted, and exposure or not to ovariectomy contributed to the lack of parity of the selected studies. Our results indicated that alendronate monotherapy negatively affects the early phase of wound healing after tooth extraction in preclinical studies, suggesting that the bone resorption process after tooth extraction in animals treated with alendronate might impair the bone healing process of the extraction socket. In conclusion, alendronate administration restrains bone resorption, thereby delaying alveolar socket healing . Future studies should be conducted to validate these findings and to better understand the effects of alendronate therapy on oral tissues

Clinical effects of systemic and topical tetracycline therapy on chronic periodontal disease.

In order to evaluate the additional effects of antimicrobials associated with conventional therapy, this study compared the clinical changes in subjects treated with scaling and root planing (SRP) alone or in combination with local or systemically administered tetracycline over time. Thirty patients with chronic periodontitis were randomly assigned to 3 groups: SRP + 500 mg of systemic tetracycline twice/day for 14 days (SRP + Tetra); SRP alone and SRP + tetracycline fibers at 4 selected sites for 10 days (SRP + Fiber). Clinical assessments were made at 6 sites/tooth at baseline, 3 and 6 months post-therapy. Two types of analyses were performed, one including all sites and other only the 4 test sites in each subject. Significant changes within and between groups were sought using Friedman, Mann-Whitney and Kruskal-Wallis tests. All therapies resulted in clinical improvement over time, which was more marked in the groups treated with tetracycline. The SRP + Tetra group had a significant lower % of sites with plaque, bleeding on probing (BOP) and deep probing pocket depth (PPD) at 3 months; higher % of sites with shallow PPD and lower % of sites with PPD = 4 - 6mm at 3 and 6 months compared to SRP alone (p< 0.05). Subjects in the SRP + Fiber group had a significant lower % of sites with BOP at 3 months and lower mean of attachment level at 6 months than the controls (p< 0.05). The adjunctive use of systemic or local tetracycline may improve the efficacy of the mechanical non-surgical therapy of chronic periodontitis

Paraganglioma gangliocítico duodenal

We present a case of a 42-year-old man with abdominal pain, obstructive jaundice and a mass in the second portion of the duodenum, near the papillary region. The patient was operated and the histological study of the specimen returned duodenal gangliocytic paraganglioma (a rare submucosal benign tumor of the duodenum). We also describe, after revision of the literature, the pathology, the diagnosis and its treatment

Microbiological evaluation of adjunctive systemic and local tetracycline administration combined with scaling and root planing in the treatment of chronic periodontitis

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