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Tetrabromobisphenol A Promotes the Osteoclastogenesis of RAW264.7 Cells Induced by Receptor Activator of NF-kappa B Ligand In Vitro

Journal of Korean Medical Science 2019년 34권 41호 p.267 ~ 267
 ( Park So-Young ) - Kyung Hee University Hospital Department of Internal Medicine

 ( Choi Eun-Mi ) - Kyung Hee University School of Medicine Department of Internal Medicine
 ( Suh Kwang-Sik ) - Kyung Hee University School of Medicine Department of Internal Medicine
 ( Kim Hyun-Sook ) - Cheongju University College of Health and Medical Sciences Department of Biomedical Laboratory Science
 ( Chin Sang-Ouk ) - Kyung Hee University Hospital Department of Internal Medicine
 ( Rhee Sang-Youl ) - Kyung Hee University School of Medicine Department of Internal Medicine
 ( Kim Deog-Yoon ) - Kyung Hee University School of Medicine Department of Nuclear Medicine
 ( Oh Seung-Joon ) - Kyung Hee University School of Medicine Department of Internal Medicine
전숙 ( Chon Suk ) - Kyung Hee University Hospital Department of Internal Medicine

Abstract


Background: Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame-retardants, is a representative persistent organic pollutants group. Studies on TBBPA toxicity have been conducted using various target cells; however, few studies have investigated TBBPA toxicity in bone cells. Therefore, this study investigated the in vitro effects of TBBPA on osteoclasts, a cell type involved in bone metabolism.

Methods: RAW264.7 cells were cultured in medium containing 50 ng/mL receptor activator of nuclear factor kappa B ligand (RANKL) and varying concentrations of TBBPA. To evaluate the effects of TBBPA on the differentiation and function of osteoclasts, osteoclast-specific gene expression, tartrate-resistant acid phosphatase (TRAP) activity, bone resorbing activity, mitochondrial membrane potential (MMP) and mitochondrial superoxide were measured.

Results: The presence of 20 μM TBBPA significantly increased TRAP activity in RANKL-stimulated RAW264.7 cells, the bone resorbing activity of osteoclasts, and the gene expression of Akt2, nuclear factor of activated T-cells cytoplasmic 1, and chloride channel voltage-sensitive 7. However, TBBPA treatment caused no change in the expression of carbonic anhydrase II, cathepsin K, osteopetrosis-associated transmembrane protein 1, Src, extracellular signal-related kinase, GAB2, c-Fos, or matrix metalloproteinase 9. Furthermore, 20 μM TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production.

Conclusion: This study suggests that TBBPA promotes osteoclast differentiation and activity. The mechanism of TBBPA-stimulated osteoclastogenesis might include increased expression of several genes involved in osteoclast differentiation and reactive oxygen species production.

키워드

Mitochondrial Function; RAW264.7 Cells; Tetrabromobisphenol A; Osteoclastogenesis
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