| Osteoblastic Responses to LPS, Glucose-oxidised LDL and Minocycline: Therapeutic Targets for Periodontal and Cardiometabolic Diseases. | |
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MedLine Citation:
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PMID: 22280224 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Objectives: To study redox responses of cultured osteoblasts, mediated by bacterial lipopolysaccharide (LPS), glucose (G), glucose-oxidised low density lipoprotein (GLDL) and minocycline (M) using radiolabelled steroid markers of redox status and wound healing. The clinical relevance of this concept in periodontitis patients with cardiometabolic risk markers is addressed. Methods: A well differentiated osteoblastic cell-line was cultured in Eagle's MEM in confluent monolayer, in 24 well multiwell plates. Radiolabelled testosterone was used as the steroid substrate. Experiments were set up with controls in the absence of agents, optimal concentrations (previously determined) of G, GLDL, LPS, M, GLDL+LPS and the latter combined with M (n = 8). At the end of a 24h incubation period, the reaction was terminated and the medium analysed for yields of the steroid metabolite 5α-dihydrotestosterone (DHT), the redox marker relevant to wound healing, the weaker androgen 4-androstenedione (4-A) and the diols. Analysis entailed thin layer chromatography and radioisotope scanning. Results: The yields of DHT showed 1.4-fold and 2.3-fold decreases in response to GLDL and LPS respectively and a 1.3-fold reduction in response to the combination, when compared with controls in the absence of agents. Minocycline stimulated the yield of DHT by 1.4-fold, and when combined with GLDL+LPS, the decreased yield was overcome and raised to 2-fold above the combination in response to the addition of minocycline (n = 8; p < 0.001), when compared with controls. The trends in the yields of 4-A and diols were inversely related to each other with increases and decreases over controls respectively, in keeping with enzymic pathways. Conclusions: Decreased yields of the oxidative stress marker DHT in response to LPS, G and GLDL were overcome in the presence of minocycline, which demonstrates its potential role as an adjunctive therapeutic agent in an environment of oxidative stress. These applications could be extrapolated to periodontal disease and co-existing cardiometabolic risk markers, in the context of its antiinflammatory and antioxidant actions relevant to healing. In this paper, recent patents relevant to adjunctive therapeutic management of periodontal disease co-existing with cardiometabolic risk markers are addressed. There have been significant advances in therapeutic interventions for overcoming oxidative stress-inducing mechanisms that are common to these disease entities. |
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Authors:
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Aruni Tilakaratne; Mena Soory |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Recent patents on endocrine, metabolic & immune drug discovery Volume: 6 ISSN: 1872-2148 ISO Abbreviation: Recent Pat Endocr Metab Immune Drug Discov Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-01-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101299743 Medline TA: Recent Pat Endocr Metab Immune Drug Discov Country: United Arab Emirates |
Other Details:
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Languages: eng Pagination: 73-84 Citation Subset: IM |
Affiliation:
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Periodontology King's College London Dental Institute King's College Dental Hospital Denmark Hill London SE5 9RW UK. mena.soory@kcl.ac.uk. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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