☆ 4.5 Article

Low dose of doxycyline promotes early differentiation of preosteoblasts by partially regulating the expression of estrogen receptors

JOURNAL OF SURGICAL RESEARCH (2012)

Journal

JOURNAL OF SURGICAL RESEARCH

Volume 178, Issue 2, Pages 737-742

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE

DOI: 10.1016/j.jss.2012.03.072

Keywords

Differentiation; Doxycycline; Estrogen receptor; Mineralization; Minocycline; Osteoblast; Tetracycline

Funding

Bioethics Expert Development Fund by the Committee for Life in the Archdiocese of Seoul

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Abstract

Background: The tetracycline (TC) family, including minocycline and doxycycline (DC), has long been used in the medical field owing to its well-characterized antimicrobial properties. Moreover, TCs have been reported to have effects on bone formation and bone metabolism. Results have shown that more new bone formation is achieved when TCs have been applied in combination with bone graft material. Methods: In the present study, the effects of TCs (TC, minocycline, and DC) on osteoprecursor cells were evaluated. The cell viability was determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Differentiation and mineralization were evaluated using an alkaline phosphatase activity test and alizarin red-S staining. In addition, the expression of proteins related to bone formation, such as estrogen receptor (ER)-alpha, bone morphogenetic protein receptor-IA, bone morphogenetic protein-2, and phospho-Smad1/5, were evaluated by using Western blot analysis. Results: The morphology of the cells seemed normal, and their viability was not affected in the treated groups compared with the control. Alkaline phosphatase activity significantly increased in cultures grown in the presence of 0.1 and 1.0 mu M of DC. No statistically significant increase in the mineralization was seen the treated groups. The results of the Western blot analysis revealed that the addition of DC upregulated ER-alpha, bone morphogenetic protein-2, and phospho-Smad1/5 expression with a statistically significant difference in ER-alpha expression. Conclusions: From our findings, it was concluded that a low dose of DC could produce positive effects on the differentiation of osteoprecursor cells at an early stage. Our results also suggested that DC has osteoinductive effects that were achieved mainly through the ER pathway by enhancing the expression of ER-alpha. (C) 2012 Elsevier Inc. All rights reserved.

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Tetracycline antibiotics: Potential anticancer drugs

Jiayu Li, Yuan Qin, Chenhao Zhao, Zhi Zhang, Zhiruo Zhou

Summary: In recent years, research on tetracycline antibiotics has shifted towards their anticancer effects. Doxycycline, minocycline, and tigecycline, approved by the FDA, have been the main focus. Evidence suggests that they can control cancer progression through various mechanisms such as anti-proliferation, anti-metastasis, and promotion of autophagy or apoptosis. These antibiotics can also be used in combination with other drugs to improve patient survival. This article introduces their mechanisms of action in different cancers, discusses combination therapies, and briefly summarizes research gaps and potential directions.

EUROPEAN JOURNAL OF PHARMACOLOGY (2023)