Calbindin-D28K mediates 25(OH)D3/VDR-regulated bone formation through MMP13 and DMP1

J Cell Biochem. 2018 Nov;119(10):8035-8047. doi: 10.1002/jcb.26722. Epub 2018 Jun 20.

Abstract

Calcium binding protein calbindin-D28K (CaBP28K) mediates the relationship between vitamin D and calcium, but its mechanism remains unclear during bone formation. The present study reports that maternal CaBP28K levels were positively correlated with paired umbilical cord CaBP28K levels. In addition, CaBP28K levels were positively correlated with the body length, and head and chest circumferences of neonates, but negatively correlated with maternal 25(OH)D3 levels. CaBP28K was also downregulated in MC3T3-E1 osteoblasts when treated with 1,25(OH)2D or VDR overexpression, but was upregulated in the femur of 1α(OH)ase(-/-) mice. Furthermore, it was found CaBP28K may influence cell differentiation and matrix formation through the regulation of DMP1 and the interaction with MMP13 in osteoblasts. This suggests that CaBP28K could be a candidate for the negative role of 1,25(OH)2D/VDR in regulating bone mass.

Keywords: 25(OH)D3/VDR; DMP1; MMP13; bone; calbindin-D28K.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Calbindin 1 / genetics
  • Calbindin 1 / metabolism*
  • Calcitriol / metabolism*
  • Cell Line
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Humans
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism*
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Osteogenesis / genetics
  • Osteogenesis / physiology*
  • Receptors, Calcitriol / metabolism*
  • Young Adult

Substances

  • Calbindin 1
  • Dmp1 protein, mouse
  • Extracellular Matrix Proteins
  • Receptors, Calcitriol
  • Matrix Metalloproteinase 13
  • Calcitriol