Interaction of dietary zinc and intracellular binding protein metallothionein in postnatal bone growth

Laura Fong, Kim Tan, Cuong Tran, Johanna Cool, Michaela Scherer, Rachel Elovaris, Peter Coyle, Bruce K. Foster, Allan M. Rofe, Cory J. Xian

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

Abstract

Zinc and its binding protein, metallothionein (MT), are important in regulating growth and development, and yet it is unclear how dietary Zn and MT interact in regulating bone growth. Here, 3.5-week female MT-I&II knockout (MT-/-) and wild type (MT+/+) mice were fed diets containing 2.5 (limiting, Zn-L), 15 or 50 mg Zn/kg (Zn adequate) for 5 or 9 weeks, and effects were analysed on structure and function of growth plate and metaphysis, two structures important for bone growth. Zn limitation did not affect bone growth in MT+/+ mice. However, MT-/- mice, having lower Zn concentrations in plasma and long bone, showed growth retardation as demonstrated by lower body length gain, shorter and smaller tibia/femur, lower chondrocyte proliferation, reduced metaphysis heights, but increased osteoclast densities on trabecular bone, particularly in mice fed Zn-L diet. Interestingly, mRNA expression of MT-I&II was induced in the growth plate of MT+/+ mice fed the Zn-L diet possibly compensating for Zn limitation. Growth plate MT-III expression increased in MT-/- mice fed the adequate Zn diet, whereas metaphyseal MT-III was significantly upregulated in MT-/- mice fed Zn-L diet, possibly as a compensatory mechanism or exacerbating effects of Zn limitation. Consistent with the increased osteoclast numbers, a higher ratio of RANKL/OPG gene expression was found in bone of mutant mice fed lower Zn diets. These results indicate that interaction between dietary Zn and endogenous MT is important for maximal bone growth, and MT is particularly important in the regulation of Zn pool for bone growth during moderate Zn limitation.

Original languageEnglish
Pages (from-to)1151-1162
Number of pages12
JournalBone
Volume44
Issue number6
DOIs
Publication statusPublished or Issued - Jun 2009

Keywords

  • Bone growth retardation
  • Growth plate
  • Metallothionein gene knockout
  • Zinc deficiency
  • Zn and metallothionein interaction

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

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