Abstract
Polychlorinated biphenyl (PCB) exposure increases the incidence and severity of skeletal diseases, but little is known about the mechanisms that mediate this relationship. We exposed zebrafish embryos to PCB1254 and assessed the changes in bone morphology protein receptor II (BMPRII), which is involved in bone formation and embryonic development, miRNA-21, for which BMPRII is a known target, and calcium metabolism. PCB1254 upregulated the expression of miR-21 and suppressed BMPRII expression. The inhibition of miR-21 reversed the downregulation of BMPRII and alleviated the PCB1254-induced loss of calcium. These findings suggest new biomarkers of developmental defects of the skeleton caused by PCBs.
Similar content being viewed by others
References
Abella V, Perez T, Scotece M, Conde J, Pirozzi C, Pino J, Lago F, Gonzalez-Gay MA, Mera A, Gomez R, Gualillo O (2016) Pollutants make rheumatic diseases worse: facts on polychlorinated biphenyls (PCBs) exposure and rheumatic diseases. Life Sci 157:140–144
Brown DS, Eames BF (2016) Emerging tools to study proteoglycan function during skeletal development. Methods Cell Biol 134:485–530
Dallaire R, Dewailly E, Ayotte P, Forget-Dubois N, Jacobson SW, Jacobson JL, Muckle G (2014) Growth in Inuit children exposed to polychlorinated biphenyls and lead during fetal development and childhood. Environ Res 134:17–23
Dietz R, Gustavson K, Sonne C, Desforges JP, Riget FF, Pavlova V, McKinney MA, Letcher RJ (2015) Physiologically-based pharmacokinetic modelling of immune, reproductive and carcinogenic effects from contaminant exposure in polar bears (Ursus maritimus) across the Arctic. Environ Res 140:45–55
Fernandez Del Ama L, Jones M, Walker P, Chapman A, Braun JA, Mohr J, Hurlstone AF (2016) Reprofiling using a zebrafish melanoma model reveals drugs cooperating with targeted therapeutics. Oncotarget
Fiandanese N, Borromeo V, Berrini A, Fischer B, Schaedlich K, Schmidt JS, Secchi C, Pocar P (2016) Maternal exposure to a mixture of di(2-ethylhexyl) phthalate (DEHP) and polychlorinated biphenyls (PCBs) causes reproductive dysfunction in adult male mouse offspring. Reproductive toxicology (Elmsford, NY) 65:123–132
Franceschetti T, Kessler CB, Lee SK, Delany AM (2013) miR-29 promotes murine osteoclastogenesis by regulating osteoclast commitment and migration. J Biol Chem 288:33347–33360
Fukushi J, Tokunaga S, Nakashima Y, Motomura G, Mitoma C, Uchi H, Furue M, Iwamoto Y (2016) Effects of dioxin-related compounds on bone mineral density in patients affected by the Yusho incident. Chemosphere 145:25–33
Gutleb AC, Schriks M, Mossink L, Berg JH, Murk AJ (2007) A synchronized amphibian metamorphosis assay as an improved tool to detect thyroid hormone disturbance by endocrine disruptors and apolar sediment extracts. Chemosphere 70:93–100
Hackl M, Heilmeier U, Weilner S, Grillari J (2016) Circulating microRNAs as novel biomarkers for bone diseases—complex signatures for multifactorial diseases? Mol Cell Endocrinol 432:83–95
Huang SY, Feng CW, Hung HC, Chakraborty C, Chen CH, Chen WF, Jean YH, Wang HM, Sung CS, Sun YM, Wu CY, Liu W, Hsiao CD, Wen ZH (2014) A novel zebrafish model to provide mechanistic insights into the inflammatory events in carrageenan-induced abdominal edema. PLoS One 9:e104414
Inose H, Ochi H, Kimura A, Fujita K, Xu R, Sato S, Iwasaki M, Sunamura S, Takeuchi Y, Fukumoto S, Saito K, Nakamura T, Siomi H, Ito H, Arai Y, Shinomiya K, Takeda S (2009) A microRNA regulatory mechanism of osteoblast differentiation. Proc Natl Acad Sci U S A 106:20794–20799
Ju L, Tang K, Guo XR, Yang Y, Zhu GZ, Lou Y (2012) Effects of embryonic exposure to polychlorinated biphenyls on zebrafish skeletal development. Mol Med Rep 5:1227–1231
Kobayashi T, Lu J, Cobb BS, Rodda SJ, McMahon AP, Schipani E, Merkenschlager M, Kronenberg HM (2008) Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci U S A 105:1949–1954
Lauby-Secretan B, Loomis D, Baan R, El Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Grosse Y, Straif K (2016) Use of mechanistic data in the IARC evaluations of the carcinogenicity of polychlorinated biphenyls and related compounds. Environ Sci Pollut Res Int 23:2220–2229
Lee DH, Steffes M, Jacobs DR (2007) Positive associations of serum concentration of polychlorinated biphenyls or organochlorine pesticides with self-reported arthritis, especially rheumatoid type, in women. Environ Health Perspect 115:883–888
Li Z, Hassan MQ, Jafferji M, Aqeilan RI, Garzon R, Croce CM, van Wijnen AJ, Stein JL, Stein GS, Lian JB (2009) Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem 284:15676–15684
Lilienthal H, Hack A, Roth-Harer A, Grande SW, Talsness CE (2006) Effects of developmental exposure to 2,2 ,4,4 ,5-pentabromodiphenyl ether (PBDE-99) on sex steroids, sexual development, and sexually dimorphic behavior in rats. Environ Health Perspect 114:194–201
Lundberg R, Lyche JL, Ropstad E, Aleksandersen M, Ronn M, Skaare JU, Larsson S, Orberg J, Lind PM (2006) Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in female goat offspring. Toxicology 228:33–40
Mizoguchi F, Murakami Y, Saito T, Miyasaka N, Kohsaka H (2013) miR-31 controls osteoclast formation and bone resorption by targeting RhoA. Arthritis research & therapy 15:R102
Oluoch-Otiego J, Oyoo-Okoth E, Kiptoo KK, Chemoiwa EJ, Ngugi CC, Simiyu G, Omutange ES, Ngure V, Opiyo MA (2016) PCBs in fish and their cestode parasites in Lake Victoria. Environ Monit Assess 188:483
Pasqualetti S, Banfi G, Mariotti M (2013) The effects of strontium on skeletal development in zebrafish embryo. Journal of trace elements in medicine and biology: organ of the Society for Minerals and Trace Elements (GMS) 27:375–379
Qin W, Zhao B, Shi Y, Yao C, Jin L, Jin Y (2009) BMPRII is a direct target of miR-21. Acta Biochim Biophys Sin 41:618–623
Shi X, Yeung LW, Lam PK, Wu RS, Zhou B (2009) Protein profiles in zebrafish (Danio rerio) embryos exposed to perfluorooctane sulfonate. Toxicological sciences: an official journal of the Society of Toxicology 110:334–340
Shibuya H, Nakasa T, Adachi N, Nagata Y, Ishikawa M, Deie M, Suzuki O, Ochi M (2013) Overexpression of microRNA-223 in rheumatoid arthritis synovium controls osteoclast differentiation. Modern rheumatology / the Japan Rheumatism Association 23:674–685
Suttamanatwong S (2016) MicroRNAs in bone development and their diagnostic and therapeutic potentials in osteoporosis. Connect Tissue Res 10:1–13
Tang P, Xiong Q, Ge W, Zhang L (2014) The role of microRNAs in osteoclasts and osteoporosis. RNA Biol 11:1355–1363
Wang YP, Hong Q, Qin DN, Kou CZ, Zhang CM, Guo M, Guo XR, Chi X, Tong ML (2012) Effects of embryonic exposure to polychlorinated biphenyls on zebrafish (Danio rerio) retinal development. Journal of applied toxicology : JAT 32:186–193
Zhou Y, Liu Y, Cheng L (2012) miR-21 expression is related to particle-induced osteolysis pathogenesis. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 30:1837–1842
Acknowledgments
This study was jointly supported by the Science and Technology Development Funds of Nanjing Medical University (2012NJMU061 & 2013NJMU095).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
All animal care and experimental procedures were approved by the Institutional Animal Care and Use Committee, Nanjing Medical University.
Funding
This study was funded by the Science and Technology Development Funds of Nanjing Medical University (2012NJMU061 & 2013NJMU095).
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Responsible editor: Henner Hollert
Rights and permissions
About this article
Cite this article
Ju, L., Zhou, Z., Jiang, B. et al. miR-21 is involved in skeletal deficiencies of zebrafish embryos exposed to polychlorinated biphenyls. Environ Sci Pollut Res 24, 886–891 (2017). https://doi.org/10.1007/s11356-016-7874-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11356-016-7874-8