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Vascular calcification and renal bone disorders.

Lu KC, Wu CC, Yen JF, Liu WC - ScientificWorldJournal (2014)

Bottom Line: Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality.These factors have roles in both promoting and inhibiting VC.In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 23148, Taiwan.

ABSTRACT
At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC.

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Related in: MedlinePlus

Calcified vessels on bone turnover in chronic kidney disease (CKD). The phenotypic osteoblast/osteocyte in calcified vessels may secrete sclerostin (SOST), secreted frizzled-related protein (sFRP), and Dickkopf-related protein 1 (DKK1), which prevent further calcification of the affected vessel. The secreted SOST and sFRP will process autocrine or paracrine effects to inhibit Wnt signaling effects on osteogenic transdifferentiation of VSMCs, which will prevent further calcification of the vessel wall. As the SOST and sFRP secreted from calcified vessel are released into circulation, they may inhibit Wnt signaling in osteoblast in the bone. This inhibition of bone osteoblasts reduces bone accretion and turnover, resulting in a fragile bone, which may also contribute elevated serum inorganic phosphates. In addition, DKK1 enhances RANKL levels, and the increased RANKL : OPG ratio activates osteoclast activity, leading to the increase of bone resorption.
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fig5: Calcified vessels on bone turnover in chronic kidney disease (CKD). The phenotypic osteoblast/osteocyte in calcified vessels may secrete sclerostin (SOST), secreted frizzled-related protein (sFRP), and Dickkopf-related protein 1 (DKK1), which prevent further calcification of the affected vessel. The secreted SOST and sFRP will process autocrine or paracrine effects to inhibit Wnt signaling effects on osteogenic transdifferentiation of VSMCs, which will prevent further calcification of the vessel wall. As the SOST and sFRP secreted from calcified vessel are released into circulation, they may inhibit Wnt signaling in osteoblast in the bone. This inhibition of bone osteoblasts reduces bone accretion and turnover, resulting in a fragile bone, which may also contribute elevated serum inorganic phosphates. In addition, DKK1 enhances RANKL levels, and the increased RANKL : OPG ratio activates osteoclast activity, leading to the increase of bone resorption.

Mentions: VC and impaired bone metabolism, the important causes of mortality and morbidity, are common in patients with CKD or osteoporosis, and in those who are aging [163]. The Wnt signaling pathway is a complicated network of several proteins that can regulate normal physiologic bone formation processes [164]. The consequence of Wnt signaling in bone is mediated by stimulation of stem cells and proliferation of preosteoblasts, induction of osteoblastogenesis, inhibition of osteoblast and osteocyte apoptosis, and attenuation of osteoclastogenesis [165, 166]. Thus, the physiological mechanisms of Wnt signaling lead to both formation and antiresorption benefits at the same time [167]. The effect of Wnt signaling depends on a transmembrane receptor complex composed of the frizzled receptor and the low-density lipoprotein receptor-related protein- (LRP-) 5 or LRP-6 coreceptors [165, 166]. Recent evidence supports the notion that there are inhibitors associated with the Wnt signaling pathway, such as sclerostin, secreted frizzled proteins 2 and 4, and Dickkopf-related protein-1 (DKK-1), that enhance osteoclast function and link VC and bone loss [168, 169] (Figure 5). Pinzone et al. stated that DKK-1 increases the osteolytic activity and decreases osteoblast differentiation [170].


Vascular calcification and renal bone disorders.

Lu KC, Wu CC, Yen JF, Liu WC - ScientificWorldJournal (2014)

Calcified vessels on bone turnover in chronic kidney disease (CKD). The phenotypic osteoblast/osteocyte in calcified vessels may secrete sclerostin (SOST), secreted frizzled-related protein (sFRP), and Dickkopf-related protein 1 (DKK1), which prevent further calcification of the affected vessel. The secreted SOST and sFRP will process autocrine or paracrine effects to inhibit Wnt signaling effects on osteogenic transdifferentiation of VSMCs, which will prevent further calcification of the vessel wall. As the SOST and sFRP secreted from calcified vessel are released into circulation, they may inhibit Wnt signaling in osteoblast in the bone. This inhibition of bone osteoblasts reduces bone accretion and turnover, resulting in a fragile bone, which may also contribute elevated serum inorganic phosphates. In addition, DKK1 enhances RANKL levels, and the increased RANKL : OPG ratio activates osteoclast activity, leading to the increase of bone resorption.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4127293&req=5

fig5: Calcified vessels on bone turnover in chronic kidney disease (CKD). The phenotypic osteoblast/osteocyte in calcified vessels may secrete sclerostin (SOST), secreted frizzled-related protein (sFRP), and Dickkopf-related protein 1 (DKK1), which prevent further calcification of the affected vessel. The secreted SOST and sFRP will process autocrine or paracrine effects to inhibit Wnt signaling effects on osteogenic transdifferentiation of VSMCs, which will prevent further calcification of the vessel wall. As the SOST and sFRP secreted from calcified vessel are released into circulation, they may inhibit Wnt signaling in osteoblast in the bone. This inhibition of bone osteoblasts reduces bone accretion and turnover, resulting in a fragile bone, which may also contribute elevated serum inorganic phosphates. In addition, DKK1 enhances RANKL levels, and the increased RANKL : OPG ratio activates osteoclast activity, leading to the increase of bone resorption.
Mentions: VC and impaired bone metabolism, the important causes of mortality and morbidity, are common in patients with CKD or osteoporosis, and in those who are aging [163]. The Wnt signaling pathway is a complicated network of several proteins that can regulate normal physiologic bone formation processes [164]. The consequence of Wnt signaling in bone is mediated by stimulation of stem cells and proliferation of preosteoblasts, induction of osteoblastogenesis, inhibition of osteoblast and osteocyte apoptosis, and attenuation of osteoclastogenesis [165, 166]. Thus, the physiological mechanisms of Wnt signaling lead to both formation and antiresorption benefits at the same time [167]. The effect of Wnt signaling depends on a transmembrane receptor complex composed of the frizzled receptor and the low-density lipoprotein receptor-related protein- (LRP-) 5 or LRP-6 coreceptors [165, 166]. Recent evidence supports the notion that there are inhibitors associated with the Wnt signaling pathway, such as sclerostin, secreted frizzled proteins 2 and 4, and Dickkopf-related protein-1 (DKK-1), that enhance osteoclast function and link VC and bone loss [168, 169] (Figure 5). Pinzone et al. stated that DKK-1 increases the osteolytic activity and decreases osteoblast differentiation [170].

Bottom Line: Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality.These factors have roles in both promoting and inhibiting VC.In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City 23148, Taiwan.

ABSTRACT
At the early stage of chronic kidney disease (CKD), the systemic mineral metabolism and bone composition start to change. This alteration is known as chronic kidney disease-mineral bone disorder (CKD-MBD). It is well known that the bone turnover disorder is the most common complication of CKD-MBD. Besides, CKD patients usually suffer from vascular calcification (VC), which is highly associated with mortality. Many factors regulate the VC mechanism, which include imbalances in serum calcium and phosphate, systemic inflammation, RANK/RANKL/OPG triad, aldosterone, microRNAs, osteogenic transdifferentiation, and effects of vitamins. These factors have roles in both promoting and inhibiting VC. Patients with CKD usually have bone turnover problems. Patients with high bone turnover have increase of calcium and phosphate release from the bone. By contrast, when bone turnover is low, serum calcium and phosphate levels are frequently maintained at high levels because the reservoir functions of bone decrease. Both of these conditions will increase the possibility of VC. In addition, the calcified vessel may secrete FGF23 and Wnt inhibitors such as sclerostin, DKK-1, and secreted frizzled-related protein to prevent further VC. However, all of them may fight back the inhibition of bone formation resulting in fragile bone. There are several ways to treat VC depending on the bone turnover status of the individual. The main goals of therapy are to maintain normal bone turnover and protect against VC.

Show MeSH
Related in: MedlinePlus