Arsenic induces cell apoptosis in cultured osteoblasts through endoplasmic reticulum stress

Journal Article · Mon Nov 30 23:00:00 EST 2009 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.08.011· OSTI ID:21344799

Chiu, Y -C ^[1]; Huang, C -F ^[2]; Chen, Y -W ^[3]; Chen, P -C ^[4]

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1. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan (China)
2. School of Chinese Medicine, China Medical University, Taichung, Taiwan (China)
3. Department of Physiology, China Medical University, Taichung, Taiwan (China)
4. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan (China)

Osteoporosis is characterized by low bone mass resulting from an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Therefore, decreased bone formation by osteoblasts may lead to the development of osteoporosis, and rate of apoptosis is responsible for the regulation of bone formation. Arsenic (As) exists ubiquitously in our environment and increases the risk of neurotoxicity, liver injury, peripheral vascular disease and cancer. However, the effect of As on apoptosis of osteoblasts is mostly unknown. Here, we found that As induced cell apoptosis in osteoblastic cell lines (including hFOB, MC3T3-E1 and MG-63) and mouse bone marrow stromal cells (M2-10B4). As also induced upregulation of Bax and Bak, downregulation of Bcl-2 and dysfunction of mitochondria in osteoblasts. As also triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosolic-calcium levels. We found that As increased the expression and activities of glucose-regulated protein 78 (GRP78) and calpain. Transfection of cells with GRP78 or calpain siRNA reduced As-mediated cell apoptosis in osteoblasts. Therefore, our results suggest that As increased cell apoptosis in cultured osteoblasts and increased the risk of osteoporosis.

• OSTI ID: 21344799
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 241; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL CELLS
ANIMAL TISSUES
APOPTOSIS
ARSENIC
BODY
BONE MARROW
CELL CONSTITUENTS
CONNECTIVE TISSUE CELLS
DIGESTIVE SYSTEM
DISEASES
ELEMENTS
ENDOPLASMIC RETICULUM
GLANDS
HEMATOPOIETIC SYSTEM
LIVER
NEOPLASMS
ORGANS
OSTEOPOROSIS
SEMIMETALS
SKELETAL DISEASES
SKELETON
SOMATIC CELLS
STRESSES
TOXICITY
VASCULAR DISEASES