Rendra LEONAS, Zairin NOOR, Hermawan Nagar RASYİD, Tita Husnitawati MADJİD, Fachry Ambia TANJUNG

Effect of lead nanoparticles inhalation on bone calcium sensing receptor, hydroxyapatite crystal, and receptor activator of nuclear factor-kappa B in rats

This study aimed to investigate whether Pb nanoparticle exposure affects the bone calcium sensing receptor (CaSR), hydroxyapatite crystal, and receptor activator of nuclear factor-kappa B (RANK) in rats exposed to subchronic and chronic inhalation. Thirty two rats were randomly divided into eight groups. One group is a non-exposed group. While three groups were exposed to nanoparticles Pb at the following doses 6.25; 12.5; or 25 mg/m3 an hour daily for 28 days. Another three groups were exposed to nanoparticles Pb at following doses 6.25; 12.5; and 25 mg/m3 one hour daily for 6 months. The expression of trabecular CaSR was significantly decreased at the all doses subchronic exposure compared to the control group (P < 0.05). The CaSR expression significantly decreased in second and third doses subchronic exposure groups compared to the control groups (P < 0.05). With subchronic exposure, the crystal size was increased in second dose group and decreased in lowest and highest doses compared to the control (untreated) group. The crystal size and c-axis were decreased in all dose chronic exposures compared to the control (untreated) group. The expression of cortical RANK was significantly lower at the two lowest dose chronic exposures compared to the control group (P < 0.05). In conclusion, Pb nanoparticle inhibit hydroxyapatite crystal growth at least a part via down regulation of CaSR and RANK

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1. Kumar V, Abbas A, Fausto N. Robbins and Cotran: pathologic basic of disease. 7 edition. Elsevier, Philadelphia, USA, 2005.

2. Ronis M, Aronson J, Gao G, Hogue W, Skinner RA, Badger TM, Lumpkin CK Jr. Skeletal effects of developmental Pb exposure in rats. Toxicoll Sci. 2001;62(2):321–9.

3. Gover RA. Nutrition and metal toxicity. Am J Clin Nutr. 1995;61(3suppl):646S-50S.

4. Wang M, Yao Y, Kuang D, Hampson DR. Activation of family C Gprotein coupled receptors by the tripeptide glutathione. J Biol Chem. 2006;281(13):8864-70.

5. Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger M, Lytton J, Hebert S. Cloning, expression, and characterization of an extracellular Ca2+ sensing receptor from bovine parathyroid. Nature. 1993;366 (6455): 575-80.

6. Handlogten M, Shirashi N, Awata H, Huang C, Miller R. Extracellular Ca2+-sensing receptor is a promiscuous divalent cation sensor that responds to lead. Am J Physiol Renal Physiol. 2000;279(6):F1083-F91.

7. Quinn S, Ye CP, Diaz R, Kifor O, Bai M, Vassilev P, Brown E. The Ca2+-sensing receptor: a target for polyamines. Am J Physiol Cell Physiol. 1997;273(4 Pt 1):C1315-23.

8. Wong BR, Josien R, Lee SY, Vologodskaia M, Steinman RM, Choi Y. The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor. J Biol Chem. 1998;273(43):28355-9.

9. Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Boyle WJ, Riggs BL. The roles of osteoprotegerin and osteoprotegerin ligand in the paracrine regulation of bone resorption. J Bone Miner Res. 2000:15(1):2-12.

10. Kanazawa K, Kudo A. Self-assembled RANK induces osteoclastogenesis ligand- independently. J Bone Miner Res. 2005;20(11):2053-60.

11. Arai F, Miyamoto T, Ohneda O, Inada T, Sudo T, Brasel K, Miyata T, Anderson DM, Suda T. Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors. J Exp Med. 1999;190(12):1741-54.

12. Kania N, Setiawan B, Widjajanto E, Nurdiana N, Widodo MA, Kusuma HC. Peroxidative index as novel marker of hydrogen peroxide involvement in lipid peroxidation from coal dust exposure. Oxidant Antioxid Med Sci. 2012;1(3):209-15.

13. Setiawan B, Darsuni A, Muttaqien F, Adiputro DL, Kania N, Nugrahenny D, Widodo MA. The effects of combined particulate matter 10 coal dust exposure and high-cholesterol diet on lipid profiles, endothelial damage, and hematopoietic stem cells in rats. J Exp Integr Med. 2013;3(3):219-23.

14. Setiawan B, Darsuni A, Muttaqien F, Widodo MA. Cholesterol lowering effect of subchronic inhalation particulate matter 10 coal dust on rats. Med-Science. 2013;2(2):500-11.

15. Noor Z, Setiawan B. Subchronic inhaled particulate matter coal dust changes bone mesostructure, mineral element and turn over markers in rats. J Exp Integr Med. 2013;3:153-8.

16. Gurel A, Armutcu F, Damatoglu S, Unalacak M, Demircan N. Evaluation of erythrocyte Na+ , K+ -ATPase and superoxide dismutase activities and malondialdehyde level alteration in coal miners. Eur J Gen Med. 2004;1(4):22-8.

17. Noor Z, Setiawan B. Subchronic inhaled particulate matter coal dust changes bone mesostructure, mineral element and turn over markers in rats. J Exp Integr Med. 2013;3(2):153-8.

18. Yamaguchi T. The calcium-sensing receptor in bone. J Bone Miner Metab. 2008;26(4):301-11.

19. Richards JB, Kavvoura FK, Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson BV, Hsu YH, Zillikens MC, Wilson SG,Mullin BH, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra BA, Pols HA, Sigurdsson G, Thorsteinsdottir U, Soranzo N, Williams FM, Zhou Y, Ralston SH, Thorleifsson G, van Duijn CM,Kiel DP, Stefansson K, Uitterlinden AG, Ioannidis JP, Spector TD; Genetic Factors for Osteoporosis Consortium. Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med. 2009;151(8):528-38.

20. Martin TJ. Osteoblast-derived PTHrP is a physiological regulator of bone formation. J Clin Invest. 2005;115(9):2322-4.

21. Ahlstrom M, Pekkinen M, Riehle U, Lamberg-Allardt C. Extracellular calcium regulates parathyroid hormone-related peptide expression in osteoblasts and osteoblast progenitor cells. Bone. 2008;42(3):482-90.

22. Klostranec JM, Chan WCW. Quantum dots in biological and biomedical research: recent progress and present challenges. J Adv Mater. 2006;18(15):1953-64.

23. Martin P. Wound healing--aiming for perfect skin regeneration. Science. 1997;276(5309):75-81.

24. Zhao X, Wu Z, Zhang Y, Gao MX, Yan YB, Cao PC, Zang Y, Lei W. Locally administrated perindopril improves healing in an ovariectomized rat tibial osteotomy model. PLoS One. 2012;7(3):e33228.

25. Boyce BF, Xing L. Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys. 2008; 473(2):139- 46.