Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease?

Abstract

Chronic kidney disease (CKD) commonly occurs with vitamin K (VK) deficiency and impaired bone mineralization. However, there are no data explaining the metabolism of endogenous VK and its role in bone mineralization in CKD. In this study, we measured serum levels of phylloquinone (VK1), menaquinone 4 and 7 (MK4, MK7), and VK-dependent proteins: osteocalcin, undercarboxylated osteocalcin (Glu-OC), and undercarboxylated matrix Gla protein (ucMGP). The carboxylated osteocalcin (Gla-OC), Glu-OC, and the expression of genes involved in VK cycle were determined in bone. The obtained results were juxtaposed with the bone mineral status of rats with CKD. The obtained results suggest that the reduced VK1 level observed in CKD rats may be caused by the accelerated conversion of VK1 to the form of menaquinones. The bone tissue possesses all enzymes, enabling the conversion of VK1 to menaquinones and VK recycling. However, in the course of CKD with hyperparathyroidism, the intensified osteoblastogenesis causes the generation of immature osteoblasts with impaired mineralization. The particular clinical significance seems to have a finding that serum osteocalcin and Glu-OC, commonly used biomarkers of VK deficiency, could be inappropriate in CKD conditions, whereas Gla-OC synthesized in bone appears to have an adverse impact on bone mineral status in this model.

Effects of Bacillus halophilus on growth, intestinal flora and metabolism of Larimichthys crocea

“…Bacteroides is the main synthetic bacteria for vitamin K. In vivo , vitamin K is mainly involved in blood coagulation. The carboxylase system dependent on vitamin K not only plays an important role in blood coagulation but is also related to the formation of the calcium binding protein osteocalcin [ 64 , 65 ]. Bacteroides can prevent or treat osteoporosis by increasing bone density [ 66 ].…”

The Potential of Vitamin K as a Regulatory Factor of Bone Metabolism—A Review

“…The undercarboxylated OC (ucOC) is an inactive form, while the active carboxylated form of OC has an increased affinity with free calcium ions and hydroxyapatite (HA), which subsequently inhibits the abnormal HA crystallization formation and cartilage mineralization speed and maintains the normal mineralization rate [61]. A previous study has shown that serum levels of ucOC may be more sensitive to VK status and can thus be used to detect subclinical VK deficiency [62]. Double-blind, randomized controlled trials reported that supplementation with ≥100 µg MK-7 in diets could improve OC γ-carboxylation status [63].…”