title: Iron overload inhibits calcification and differentiation of ATDC5 cells.
abstract: There is a little information about the effects of iron overload on cartilage metabolism. In the present study, we examined the effects of excess iron on the differentiation and mineralization of cultured chondrocytes, ATDC5 cells. We used ferric ammonium citrate (FAC) as a ferric ion donor and desferrioxamine (DFO) as a ferric ion chelator. Neither chemical affected the production of proteoglycan, a marker of an early stage of ATDC5 differentiation. In contrast, FAC inhibited the deposition of calcium, a late-stage event in chondrocyte differentiation, by ATDC5 cells in a dose-dependent manner, and DFO accelerated it. Energy dispersive X-ray spectroscopy/scanning electron microscope analysis revealed that the levels of iron and calcium in cells treated with FAC were increased and decreased, respectively. Furthermore, FAC inhibited the expression of matrix metalloproteinase 13 mRNA, another marker of late-stage chondrocyte differentiation. In addition, we found that the heavy and light chains of ferritin were expressed specifically at a late stage of ATDC5 differentiation, and the levels of both proteins were enhanced by the addition of iron. These results suggest that iron overload might give rise to osteopenia and arthritis by inhibiting chondrocyte differentiation and mineralization.
authors: Department of Biological Sciences, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors: Tomoya
authors: T
authors: Ohno
authors: Nobuaki
authors: N
authors: Hashimoto
authors: Kenichi
authors: K
authors: Mitsui
authors: Hiroyuki
authors: H
authors: Nishimura
authors: Hiromi
authors: H
authors: Hagiwara
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000378:metabolism / Q000494:pharmacology; D005293:Ferritins / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D007501:Iron / Q000378:metabolism / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008855:Microscopy, Electron, Scanning; D011509:Proteoglycans / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017262:Siderophores / Q000494:pharmacology; D013052:Spectrometry, X-Ray Emission; D013997:Time Factors
chemical_list: D024043:Collagen Type II; D024121:Collagen Type X; D005290:Ferric Compounds; D011509:Proteoglycans; D000644:Quaternary Ammonium Compounds; D017262:Siderophores; D005293:Ferritins; D007501:Iron; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D003676:Deferoxamine; D002118:Calcium; C013531:ferric ammonium citrate