Effects of Arsenic on Osteoblast Differentiation in Vitro and on Bone Mineral Density and Microstructure in Rats

Autor:	Ding-Cheng Chan, Keh-Sung Tsai, Shing-Hwa Liu, Cheng-Tien Wu, Tung-Ying Lu, Rong-Sen Yang
Jazyk:	angličtina
Rok vydání:	2014
Předmět:	inorganic chemicals Male Bone density Health Toxicology and Mutagenesis Dentistry chemistry.chemical_element Bone Morphogenetic Protein 2 Core Binding Factor Alpha 1 Subunit Bone morphogenetic protein 2 Arsenicals Bone and Bones Hazardous Substances Arsenic chemistry.chemical_compound Arsenic Trioxide Bone Density Osteogenesis medicine Animals Arsenic trioxide Extracellular Signal-Regulated MAP Kinases Bone mineral Osteoblasts integumentary system Arsenic toxicity business.industry Chemistry Research Drinking Water Public Health Environmental and Occupational Health Osteoblast Cell Differentiation Oxides In vitro Rats medicine.anatomical_structure Environmental chemistry business
Zdroj:	Environmental Health Perspectives
ISSN:	1552-9924 0091-6765
Popis:	Background: Arsenic is a ubiquitous toxic element and is known to contaminate drinking water in many countries. Several epidemiological studies have shown that arsenic exposure augments the risk of bone disorders. However, the detailed effect and mechanism of inorganic arsenic on osteoblast differentiation of bone marrow stromal cells and bone loss still remain unclear. Objectives: We investigated the effects and mechanism of arsenic on osteoblast differentiation in vitro and evaluated bone mineral density (BMD) and bone microstructure in rats at doses relevant to human exposure from drinking water. Methods: We used a cell model of rat primary bone marrow stromal cells (BMSCs) and a rat model of long-term exposure with arsenic-contaminated drinking water, and determined bone microstructure and BMD in rats by microcomputed tomography (μCT). Results: We observed significant attenuation of osteoblast differentiation after exposure of BMSCs to arsenic trioxide (0.5 or 1 μM). After arsenic treatment during differentiation, expression of runt-related transcription factor-2 (Runx2), bone morphogenetic protein-2 (BMP-2), and osteocalcin in BMSCs was inhibited and phosphorylation of enhanced extracellular signal-regulated kinase (ERK) was increased. These altered differentiation-related molecules could be reversed by the ERK inhibitor PD98059. Exposure of rats to arsenic trioxide (0.05 or 0.5 ppm) in drinking water for 12 weeks altered BMD and microstructure, decreased Runx2 expression, and increased ERK phosphorylation in bones. In BMSCs isolated from arsenic-treated rats, osteoblast differentiation was inhibited. Conclusions: Our results suggest that arsenic is capable of inhibiting osteoblast differentiation of BMSCs via an ERK-dependent signaling pathway and thus increasing bone loss. Citation: Wu CT, Lu TY, Chan DC, Tsai KS, Yang RS, Liu SH. 2014. Effects of arsenic on osteoblast differentiation in vitro and on bone mineral density and microstructure in rats. Environ Health Perspect 122:559–565; http://dx.doi.org/10.1289/ehp.1307832
Databáze:	OpenAIRE
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