Zinc Homeostasis in Bone: Zinc Transporters and Bone Diseases

Int J Mol Sci. 2020 Feb 12;21(4):1236. doi: 10.3390/ijms21041236.


Zinc is an essential micronutrient that plays critical roles in numerous physiological processes, including bone homeostasis. The majority of zinc in the human body is stored in bone. Zinc is not only a component of bone but also an essential cofactor of many proteins involved in microstructural stability and bone remodeling. There are two types of membrane zinc transporter proteins identified in mammals: the Zrt- and Irt-like protein (ZIP) family and the zinc transporter (ZnT) family. They regulate the influx and efflux of zinc, accounting for the transport of zinc through cellular and intracellular membranes to maintain zinc homeostasis in the cytoplasm and in intracellular compartments, respectively. Abnormal function of certain zinc transporters is associated with an imbalance of bone homeostasis, which may contribute to human bone diseases. Here, we summarize the regulatory roles of zinc transporters in different cell types and the mechanisms underlying related pathological changes involved in bone diseases. We also present perspectives for further studies on bone homeostasis-regulating zinc transporters.

Keywords: ZIP; ZnT; bone diseases; bone homeostasis; osteoclastogenesis; osteogenesis; zinc.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport / physiology*
  • Bone Diseases / metabolism*
  • Bone Remodeling
  • Bone and Bones / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cation Transport Proteins / metabolism
  • Cytoplasm / metabolism
  • Homeostasis / physiology*
  • Humans
  • Mammals
  • Osteogenesis
  • Repressor Proteins / metabolism
  • Zinc / metabolism*


  • Carrier Proteins
  • Cation Transport Proteins
  • Repressor Proteins
  • ZGPAT protein, human
  • zinc-binding protein
  • Zinc