Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease?
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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Nutrients |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6643/14/19/4082 |
| _version_ | 1797477542791217152 |
|---|---|
| author | Marta Ziemińska Dariusz Pawlak Beata Sieklucka Katarzyna Chilkiewicz Krystyna Pawlak |
| author_facet | Marta Ziemińska Dariusz Pawlak Beata Sieklucka Katarzyna Chilkiewicz Krystyna Pawlak |
| author_sort | Marta Ziemińska |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T21:20:10Z |
| format | Article |
| id | doaj.art-ba9f243af8bb49578b9b694a161890d1 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T21:20:10Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-ba9f243af8bb49578b9b694a161890d12023-11-23T21:25:20ZengMDPI AGNutrients2072-66432022-10-011419408210.3390/nu14194082Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease?Marta Ziemińska0Dariusz Pawlak1Beata Sieklucka2Katarzyna Chilkiewicz3Krystyna Pawlak4Department of Monitored Pharmacotherapy, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, PolandDepartment of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, PolandDepartment of Pharmacodynamics, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, PolandDepartment of Monitored Pharmacotherapy, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, PolandDepartment of Monitored Pharmacotherapy, Medical University of Bialystok, Mickiewicza 2C Str., 15-222 Bialystok, PolandChronic 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.https://www.mdpi.com/2072-6643/14/19/4082bone mineral statuschronic kidney disease (CKD)genes of vitamin VK cyclevitamin K (VK)VK-dependent proteins5/6 nephrectomy model |
| spellingShingle | Marta Ziemińska Dariusz Pawlak Beata Sieklucka Katarzyna Chilkiewicz Krystyna Pawlak Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease? Nutrients bone mineral status chronic kidney disease (CKD) genes of vitamin VK cycle vitamin K (VK) VK-dependent proteins 5/6 nephrectomy model |
| title | Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease? |
| title_full | Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease? |
| title_fullStr | Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease? |
| title_full_unstemmed | Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease? |
| title_short | Vitamin K-Dependent Carboxylation of Osteocalcin in Bone—Ally or Adversary of Bone Mineral Status in Rats with Experimental Chronic Kidney Disease? |
| title_sort | vitamin k dependent carboxylation of osteocalcin in bone ally or adversary of bone mineral status in rats with experimental chronic kidney disease |
| topic | bone mineral status chronic kidney disease (CKD) genes of vitamin VK cycle vitamin K (VK) VK-dependent proteins 5/6 nephrectomy model |
| url | https://www.mdpi.com/2072-6643/14/19/4082 |
| work_keys_str_mv | AT martazieminska vitaminkdependentcarboxylationofosteocalcininboneallyoradversaryofbonemineralstatusinratswithexperimentalchronickidneydisease AT dariuszpawlak vitaminkdependentcarboxylationofosteocalcininboneallyoradversaryofbonemineralstatusinratswithexperimentalchronickidneydisease AT beatasieklucka vitaminkdependentcarboxylationofosteocalcininboneallyoradversaryofbonemineralstatusinratswithexperimentalchronickidneydisease AT katarzynachilkiewicz vitaminkdependentcarboxylationofosteocalcininboneallyoradversaryofbonemineralstatusinratswithexperimentalchronickidneydisease AT krystynapawlak vitaminkdependentcarboxylationofosteocalcininboneallyoradversaryofbonemineralstatusinratswithexperimentalchronickidneydisease |