title: Effect of therapeutic levels of doxycycline and minocycline in the proliferation and differentiation of human bone marrow osteoblastic cells.
abstract: Semi-synthetic tetracyclines (TCs) have been reported to reduce pathological bone resorption through several mechanisms, although their effect over bone physiological metabolism is not yet fully understood. The present study aims at evaluate the behaviour of osteoblastic-induced human bone marrow cells regarding proliferation and functional activity, in the presence of representative therapeutic concentrations of doxycycline and minocycline. First passage human osteoblastic bone marrow cells were cultured for 35 days in conditions known to favor osteoblastic differentiation. Doxycycline (1-25 micro g/ml) or minocycline (1-50 micro g/ml) were added continuously, with the culture medium, twice a week with every medium change. Cultures were characterised at several time points for cell proliferation and function. Present data showed that 1 micro g/ml of both tetracyclines, level representative of that attained in plasma and crevicular fluid with the standard therapeutic dosage, increased significantly the proliferation of human bone marrow osteoblastic cells without altering their specific phenotype and functional activity. Long-term exposure to these TCs induced a significant increase in the number of active osteoblastic cells that yielded a proportional amount of a normal mineralised matrix, suggesting a potential application in therapeutic approaches aiming to increase bone formation. The presence of higher levels of these agents led to a dose-dependent deleterious effect over cell culture, delaying cell proliferation and differentiation.
authors.affiliation: Laboratório de Farmacologia e Biocompatibilidade Celular, Faculdade de Medicina Dentária, Universidade do Porto, Rua Dr Manuel Pereira da Silva, Porto, Portugal.
authors.forename: Pedro Sousa
authors.initials: PS
authors.lastname: Gomes
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Fernandes
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008911:Minocycline / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure; D010758:Phosphorus / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D010758:Phosphorus; D000469:Alkaline Phosphatase; D008911:Minocycline; D004318:Doxycycline; D002118:Calcium