Ferritin ferroxidase activity: A potent inhibitor of osteogenesis

Abolfazl Zarjou, V. Jeney, Paolo Arosio, Maura Poli, Erzsébet Zavaczki, G. Balla, J. Balla

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Hemochromatosis is a known cause of osteoporosis, and iron overload has deleterious effects on bone. Although iron overload and its association with osteoporosis has long been recognized, the pathogenesis and exact role of iron have been undefined. Bone is an active tissue with constant remodeling capacity. Osteoblast (OB) development and maturation are under the influence of core binding factor α-1 (CBF-α1), which induces expression of OB-specific genes, including alkaline phosphatase, an important enzyme in early osteogenesis, and osteocalcin, a noncollagenous protein deposited within the osteoid. This study investigates the mechanism by which iron inhibits human OB activity, which in vivo may lead to decreased mineralization, osteopenia, and osteoporosis. We demonstrate that iron-provoked inhibition of OB activity is mediated by ferritin and its ferroxidase activity. We confirm this notion by using purified ferritin H-chain and ceruloplasmin, both known to possess ferroxidase activity that inhibited calcification, whereas a site-directed mutant of ferritin H-chain lacking ferroxidase activity failed to provide any inhibition. Furthermore, we are reporting that such suppression is not restricted to inhibition of calcification, but OB-specific genes such as alkaline phosphatase, osteocalcin, and CBF-α1 are all downregulated by ferritin in a dose-responsive manner. This study corroborates that iron decreases mineralization and demonstrates that this suppression is provided by iron-induced upregulation of ferritin. In addition, we conclude that inhibition of OB activity, mineralization, and specific gene expression is attributed to the ferroxidase activity of ferritin.

Original languageEnglish
Pages (from-to)164-172
Number of pages9
JournalJournal of Bone and Mineral Research
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2010

Fingerprint

Ceruloplasmin
Ferritins
Osteoblasts
Osteogenesis
Iron
Core Binding Factors
Apoferritins
Osteoporosis
Iron Overload
Osteocalcin
Alkaline Phosphatase
Bone and Bones
Hemochromatosis
Metabolic Bone Diseases
Human Activities
Genes
Up-Regulation
Down-Regulation
Gene Expression
Enzymes

Keywords

  • Ferritin
  • Ferroxidase activity
  • Hemochromatosis
  • Iron
  • Osteoporosis

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Ferritin ferroxidase activity : A potent inhibitor of osteogenesis. / Zarjou, Abolfazl; Jeney, V.; Arosio, Paolo; Poli, Maura; Zavaczki, Erzsébet; Balla, G.; Balla, J.

In: Journal of Bone and Mineral Research, Vol. 25, No. 1, 01.2010, p. 164-172.

Research output: Contribution to journalArticle

Zarjou, Abolfazl ; Jeney, V. ; Arosio, Paolo ; Poli, Maura ; Zavaczki, Erzsébet ; Balla, G. ; Balla, J. / Ferritin ferroxidase activity : A potent inhibitor of osteogenesis. In: Journal of Bone and Mineral Research. 2010 ; Vol. 25, No. 1. pp. 164-172.
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