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

  • Park, So Young1
  • Choi, Eun Mi2
  • Suh, Kwang Sik2
  • Kim, Hyun Sook3
  • Chin, Sang Ouk1, 2
  • Rhee, Sang Youl1, 2
  • Kim, Deog Yoon4
  • Oh, Seungjoon1, 2
  • Chon, Suk1, 5
  • 1 Department of Endocrinology & Metabolism, Kyung Hee University Hospital, Seoul, Korea. , (North Korea)
  • 2 Department of Endocrinology & Metabolism, Kyung Hee University School of Medicine, Seoul, Korea. , (North Korea)
  • 3 Department of Biomedical Laboratory Science, College of Health and Medical Sciences, Cheongju University, Cheongju, Korea. , (North Korea)
  • 4 Department of Nuclear Medicine, Kyung Hee University School of Medicine, Seoul, Korea. , (North Korea)
  • 5 Department of Endocrinology & Metabolism, Kyung Hee University School of Medicine, Seoul, Korea. [email protected] , (North Korea)
Published Article
Journal of Korean medical science
Publication Date
Oct 28, 2019
DOI: 10.3346/jkms.2019.34.e267
PMID: 31650720


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. 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. The presence of 20 μ 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 μ TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production. 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. © 2019 The Korean Academy of Medical Sciences.

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