Calcium Supplement Derived from Gallus gallus domesticus Promotes BMP-2/RUNX2/SMAD5 and Suppresses TRAP/RANK Expression through MAPK Signaling Activation

Nutrients. 2017 May 17;9(5):504. doi: 10.3390/nu9050504.


The present study evaluated the effects of a calcium (Ca) supplement derived from Gallus gallus domesticus (GD) on breaking force, microarchitecture, osteogenic differentiation and osteoclast differentiation factor expression in vivo in Ca-deficient ovariectomized (OVX) rats. One percent of Ca supplement significantly improved Ca content and bone strength of the tibia. In micro-computed tomography analysis, 1% Ca supplement attenuated OVX- and low Ca-associated changes in bone mineral density, trabecular thickness, spacing and number. Moreover, 1% Ca-supplemented diet increased the expression of osteoblast differentiation marker genes, such as bone morphogenetic protein-2, Wnt3a, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin and collagenase-1, while it decreased the expression of osteoclast differentiation genes, such as thrombospondin-related anonymous protein, cathepsin K and receptor activator of nuclear factor kappa B. Furthermore, 1% Ca-supplemented diet increased the levels of phosphorylated extracellular signal-regulated kinase and c-Jun N-terminal kinase. The increased expression of osteoblast differentiation marker genes and activation of mitogen-activated protein kinase signaling were associated with significant increases in trabecular bone volume, which plays an important role in the overall skeletal strength. Our results demonstrated that 1% Ca supplement inhibited osteoclastogenesis, stimulated osteoblastogenesis and restored bone loss in OVX rats.

Keywords: calcium; differentiation; osteoporosis; ovariectomy rat.

MeSH terms

  • Animals
  • Bone Density / drug effects
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism*
  • Bone and Bones / chemistry*
  • Calcium / administration & dosage*
  • Chickens*
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • MAP Kinase Signaling System / physiology
  • Osteoporosis / metabolism
  • Osteoporosis / prevention & control*
  • Ovariectomy
  • Rats
  • Rats, Wistar
  • Receptor Activator of Nuclear Factor-kappa B / genetics
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Smad5 Protein / genetics
  • Smad5 Protein / metabolism
  • Tartrate-Resistant Acid Phosphatase / genetics
  • Tartrate-Resistant Acid Phosphatase / metabolism


  • Bmp2 protein, rat
  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • Receptor Activator of Nuclear Factor-kappa B
  • Runx2 protein, rat
  • Smad5 Protein
  • Smad5 protein, rat
  • Tartrate-Resistant Acid Phosphatase
  • Calcium