Zinc deficiency decreases osteoblasts and osteoclasts associated with the reduced expression of Runx2 and RANK

Bone. 2011 Dec;49(6):1152-9. doi: 10.1016/j.bone.2011.08.019. Epub 2011 Aug 26.


The effects of Zinc(Zn)-deficiency on the function and differentiation of osteoblasts and osteoclasts were investigated in vivo using rats, which were fed a Zn-adequate (control) or Zn-free diet (ZD) or pair-fed a Zn-adequate diet (PF) for 3 weeks. Levels of Zn, insulin, insulin-like growth factor I (IGF-I), and osteoclacin in serum and the activities and numbers of osteoblasts and osteoclasts in bone decreased in ZD rats compared with the control and PF rats. The frequency analyses showed that the precursors of osteoblasts and osteoclasts decreased in bone marrow of ZD, but not PF, rats. The expression of receptor for activation of NF-κB (RANK) decreased with the Zn-deficiency, although RANK ligand, osteoprotegerin, macrophage colony-stimulating factor, and c-fms levels were unaltered. The protein level of a transcription factor MITF, but not PU.1, decreased. The expression of Runx2 decreased associated with the decrease in β-catenin protein and the suppression of glycogen synthase kinase 3β (GSK3β) inhibition and Akt activation. The gene expression of the insulin receptor, IGF-I and the IGF-I receptor was decreased with a reduced level of transcription factor SP-1. These results suggested that a deficiency of Zn decreased osteoclastogenesis associated with the reduced expression of RANK through a decrease in MITF protein, and osteoblastogenesis associated with the reduced expression of Runx2 through the inhibition of Wnt/β-catenin signaling via the suppression of GSK3β inhibition and Akt activation preceded by the reduced level of SP-1 protein.

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Biomarkers / metabolism
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism
  • Bone and Bones / metabolism
  • Cell Differentiation / genetics
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Female
  • Femur / cytology
  • Femur / enzymology
  • Isoenzymes / metabolism
  • Osteoblasts / metabolism*
  • Osteoclasts / metabolism*
  • Osteogenesis / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor Activator of Nuclear Factor-kappa B / metabolism*
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Staining and Labeling
  • Tartrate-Resistant Acid Phosphatase
  • Transcription Factors / metabolism
  • Zinc / deficiency*
  • Zinc / metabolism


  • Biomarkers
  • Core Binding Factor Alpha 1 Subunit
  • Isoenzymes
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • Runx2 protein, rat
  • Transcription Factors
  • Receptor, Insulin
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Zinc