Abstract
Although zinc (Zn) is known to participate in bone formation, its exact role in the remodeling of this tissue has not been fully clarified. The present study was designed to investigate whether Zn has a role at the resorptive sites in vitro. We investigated the migration of osteoblastic MC3T3-E1 cells in response to Zn using a Boyden chamber assay. Exposure of MC3T3-E1 cells to Zn stimulated the migration of MC3T3-E1 cells. Checkerboard analysis revealed that the migration of MC3T3-E1 cells toward Zn was a directional (chemotaxis) rather than a random (chemokinesis) motion.
Pretreatment of MC3T3-E1 cells with pertussis toxin completely blocked the chemotactic response of cells to Zn, indicating that it is mediated by G-protein-coupled receptors. Because the bone is one of the major Zn storage sites, we suggest that Zn released from bone-resorptive sites plays an important role in the recruitment of osteoblasts and bone renewal.
Similar content being viewed by others
References
K. T. Suzuki and E. Kobayashi, Age- and sex-related changes in concentration of seven elements (Ca, Cu, Fe, Mg, P, S, and Zn) in tissues and bodily fluids of rats, Biomed. Res. Trace Elements 5, 101–111 (1994).
H. S. Hsieh and J. M. Navia, Zinc deficiency and bone formation in guinea pig alveolar implants, J. Nutr. 110, 1581–1588 (1980).
S. J. Jones, C. Gray, and A. Boyde, Stimulation of bone resorption-repair coupling in vitro, Anat. Embryol. 190, 339–349 (1994).
A. M. Parfitt and B. Chir, Bone remodeling and bone loss: understanding the pathophysiology of osteoporosis, Clin. Obstet. Gynecol. 30, 789–811 (1987).
R. O. C. Oreffo, G. R. Mundy, S. M. Seyedin, and L. F. Bonewald, Activation of the bone-derived latent TGF beta complex by isolated osteoclasts, Biochem. Biophys. Res. Commun. 158, 817–823 (1989).
E. Canalis, T. McCarthy, and M. Centrella, Growth factors and the regulation of bone remodeling, J. Clin. Invest. 81, 277–281 (1988).
J. Pfeilschifter, O. Wolf, A. Naumann, H. W. Minne, G. R. Mundy, and R. Ziegler, Chemotactic response of osteoblastlike cells to transforming growth factor β, J. Bone Miner. Res. 5, 825–830 (1990).
T. Tsukamoto, T. Matsui, M. Fukase, and T. Fujita, Platelet-derived growth factor B chain homodimer enhances chemotaxis and DNA synthesis in normal osteoblast-like cells (MC3T3-E1), Biochem. Biophys. Res. Commun. 175, 745–751 (1991).
V. Kundra, J. A. Escobedo, A, Kazlauskas, H. K. Kim, S. G. Rhee, L. T. Williams, et al., Regulation of chemotaxis by the platelet-derived growth factor receptor-β, Nature 367, 474–476 (1994).
T. Sugimoto, M. Kanatani, J. Kano, H. Kaji, T. Tsukamoto, T. Yamaguchi, et al., Effects of high calcium concentration on the functions and interactions of osteoblastic cells and monocytes and on the formation of osteoclast-like cells, J. Bone Miner. Res. 8, 1445–1452 (1993).
S. L. Godwin and S. P. Soltoff, Extracellular calcium and platelet-derived growth factor promote receptor-mediated chemotaxis in osteoblasts through different signaling pathways, J. Biol. Chem. 272, 11,307–11,312 (1997).
J. E. Hartle, II, V. Prpic, S. R. Siddhanti, R. F. Spurney, and L. D. Quarles, Differential regulation of receptor-stimulated cyclic adenosine monophosphate production by polyvalent cations in MC3T3-E1 osteoblasts, J. Bone Miner. Res. 11, 789–799 (1996).
S. Hirano, T. Asami, N. Kodama, and K. T. Suzuki, Correlation between inflammatory cellular responses and chemotactic activity in bronchoalveolar lavage fluid following intratracheal instillation of nickel sulfate in rats, Arch. Toxicol. 68, 444–449 (1994).
T. A. Fields and P. J. Casey, Signalling functions and biochemical properties of pertussis toxin-resistant G-proteins, Biochem. J. 321, 561–571 (1997).
M. Yamaguchi and R. Yamaguchi, Action of zinc on bone metabolism in rats, Biochem. Pharmacol. 35, 773–777 (1986).
D. Riccardi, J. Park, W-S. Lee, G. Gamba, E. M. Brown, and S. C. Hebert, Cloning and functional expression of a rat kidney extracellular calcium/polyvalent cation-sensing receptor, Proc. Natl. Acad. Sci. USA 92, 131–135 (1995).
Y. Kanai and M. A. Hediger, Primary structure and functional characterization of a high-affinity glutamate transporter, Nature 360, 467–471 (1992).
E. M. Brown, G. Gamba, D. Riccardi, M. Lombardi, R. Butters, O. Kifor, et al., Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid, Nature 366, 575–580 (1993).
M. Ruat, M. E. Molliver, A. M. Snowman, and S. H. Snyder, Calcium sensing receptor: molecular cloning in rat and localization to nerve terminals, Proc. Natl. Acad. Sci. USA 92, 3161–3165 (1995).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kanno, S., Anuradha, C.D. & Hirano, S. Chemotactic responses of osteoblastic MC3T3-E1 cells toward zinc chloride. Biol Trace Elem Res 83, 49–55 (2001). https://doi.org/10.1385/BTER:83:1:49
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/BTER:83:1:49