Vitamin K‑dependent proteins involved in bone and cardiovascular health (Review)

Mol Med Rep. 2018 Jul;18(1):3-15. doi: 10.3892/mmr.2018.8940. Epub 2018 Apr 27.


In postmenopausal women and elderly men, bone density decreases with age and vascular calcification is aggravated. This condition is closely associated with vitamin K2 deficiency. A total of 17 different vitamin K‑dependent proteins have been identified to date. Vitamin K‑dependent proteins are located within the bone, heart and blood vessels. For instance, carboxylated osteocalcin is beneficial for bone and aids the deposition of calcium into the bone matrix. Carboxylated matrix Gla protein effectively protects blood vessels and may prevent calcification within the vascular wall. Furthermore, carboxylated Gla‑rich protein has been reported to act as an inhibitor in the calcification of the cardiovascular system, while growth arrest‑specific protein‑6 protects endothelial cells and vascular smooth muscle cells, resists apoptosis and inhibits the calcification of blood vessels by inhibiting the apoptosis of vascular smooth muscle cells. In addition, periostin may promote the differentiation, aggregation, adhesion and proliferation of osteoblasts. Periostin also occurs in the heart and may be associated with the reconstruction of heart function. These vitamin K‑dependent proteins may exert their functions following γ‑carboxylation with vitamin K, and different vitamin K‑dependent proteins may exhibit synergistic effects or antagonistic effects on each other. In the cardiovascular system with vitamin K antagonist supplement or vitamin K deficiency, calcification occurs in the endothelium of blood vessels and vascular smooth muscle cells are transformed into osteoblast‑like cells, a phenomenon that resembles bone growth. Both the bone and cardiovascular system are closely associated during embryonic development. Thus, the present study hypothesized that embryonic developmental position and tissue calcification may have a certain association for the bone and the cardiovascular system. This review describes and briefly discusses several important vitamin K‑dependent proteins that serve an important role in bone and the cardiovascular system. The results of the review suggest that the vascular calcification and osteogenic differentiation of vascular smooth muscle cells may be associated with the location of the bone and cardiovascular system during embryonic development.

Publication types

  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / metabolism*
  • Aging / pathology
  • Bone Density*
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoporosis, Postmenopausal / metabolism*
  • Osteoporosis, Postmenopausal / pathology
  • Vitamin K / metabolism*


  • Vitamin K