High phosphorus diet induces vascular calcification, a related decrease in bone mass and changes in the aortic gene expression

Román-García, Pablo; Carrillo-López, Natalia; Fernández-Martín, José Luis; Naves-Díaz, Manuel; Ruiz-Torres, María Piedad; Cannata-Andía, Jorge B.

doi:10.1016/j.bone.2009.09.006

Cited by 139 publications

(97 citation statements)

References 49 publications

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“…Chondrogenic differentiation of aortic smooth muscle cells was also detected in mice lacking matrix ␥-carboxyglutamic acid (Gla) protein, which typically develop medial calcifications, as indicated by the induction of collagen II expression 45 and the lack of expression of Msh homebox (msx)-2, osx, Wnt3a, and Wnt7a, 23 factors promoting osteoblast differentiation. Furthermore, our results are in line with the recent results of Roman-Garcia et al, 46 who found a significant induction of secreted frizzled related proteins 1, 2, and 4, inhibitors of the Wnt/␤-catenin signaling pathway, in the calcified aorta of 7/8 nephrectomized rats. Our observation of chondrocyte-specific proteins induced in arteries from transplant donors with medial calcification 22 and the finding of cartilage metaplasia in lowerextremity arteries with extensive intima and medial calcifications of 2 diabetic patients with renal failure 47 suggest that chondrocyte differentiation is a more general mechanism underlying medial calcification, which also occurs in humans.…”

Section: Discussionsupporting

confidence: 93%

Chondrocyte Rather Than Osteoblast Conversion of Vascular Cells Underlies Medial Calcification in Uremic Rats

Neven

Persy

Dauwe

et al. 2010

ATVB

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Objective-To investigate cell biological changes in calcified aortas of rats that experienced chronic renal failure. Methods and Results-Vascular smooth muscle cells have the potential to transdifferentiate to either chondrocytes or osteoblasts, depending on the molecular pathways that are stimulated. Uremia-related medial calcification was induced by feeding rats an adenine low-protein diet for 4 weeks. Aortic calcification was evaluated biochemically and histochemically and with in vivo micro-computed tomographic scanning. Immunohistochemistry and RT-PCR were applied to analyze the time-dependent aortic expression of molecules involved in the segregation between the chondrocyte versus osteoblast differentiation pathway. After 4 weeks, 85% of the uremic rats had developed distinct aortic medial calcification, which increased to severely calcified lesions during further follow-up. The calcification process was accompanied by a significant time-dependent increase in the expression of the chondrocyte-specific markers sex determining region Y-box 9 (sox9), collagen II, and aggrecan and a nonsignificant trend toward enhanced core binding factor alpha 1 (cbfa1), and collagen I. The expression of the osteoblast marker osterix and both lipoprotein receptor-related protein 6 and ␤-catenin, molecules of the wingless-type MMTV integration site family member (Wnt)/␤-catenin pathway induced during osteoblast differentiation, was suppressed. Conclusion-In the aorta of uremic rats, medial smooth muscle cells acquire a chondrocyte rather than osteoblast phenotype during the calcification process.

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Section: Discussionsupporting

confidence: 93%

Chondrocyte Rather Than Osteoblast Conversion of Vascular Cells Underlies Medial Calcification in Uremic Rats

Neven

Persy

Dauwe

et al. 2010

ATVB

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“…Previous studies have shown in rats that just CRF is not enough to induce vascular calcification. In fact, other additional stimuli are necessary, such as an HPD 21,22 or calcitriol. 23 In addition, rats with normal renal function under the same stimulus may exhibit certain alterations in serum, but they do not calcify, despite an HPD.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs 29b, 133b, and 211 Regulate Vascular Smooth Muscle Calcification Mediated by High Phosphorus

Panizo

Naves-Díaz

Carrillo-López

et al. 2016

Journal of the American Society of Nephrology

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Vascular calcification is a frequent cause of morbidity and mortality in patients with CKD and the general population. The common association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. Because microRNAs (miRs) are involved in the transdifferentiation of vascular smooth muscle cells into osteoblast-like cells, we investigated whether miRs implicated in osteoblast differentiation and bone formation are involved in vascular calcification. Different levels of uremia, hyperphosphatemia, and aortic calcification were induced by feeding nephrectomized rats a normal or highphosphorus diet for 12 or 20 weeks, at which times the levels of eight miRs (miR-29b, miR-125, miR-133b, miR-135, miR-141, miR-200a, miR-204, and miR-211) in the aorta were analyzed. Compared with controls and uremic rats fed a normal diet, uremic rats fed a high-phosphorous diet had lower levels of miR-133b and miR-211 and higher levels of miR-29b that correlated respectively with greater expression of osteogenic RUNX2 and with lower expression of several inhibitors of osteoblastic differentiation. Uremia per se mildly reduced miR-133b levels only. Similar results were obtained in two in vitro models of vascular calcification (uremic serum and highcalcium and -phosphorus medium), and experiments using antagomirs and mimics to modify miR-29b, miR-133b, and miR-211 expression levels in these models confirmed that these miRs regulate the calcification process. We conclude that miR-29b, miR-133b, and miR-211 have direct roles in the vascular smooth muscle calcification induced by high phosphorus and may be new therapeutic targets in the management of vascular calcification.

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“…Таким обра-зом, сигнальный путь Wnt не только играет главную роль в метаболизме кости, но также вовлечен в процессы каль-цификации медии артерий и клапанов сердца [4,12]. Установлено, что склеростин (гликопротеин, секретируе-мый остеоцитами) является блокатором сигнального пути Wnt и может быть важным регулятором минерализации при развитии кальцификации сердца и сосудов, а также может оказывать повреждающее действие на метаболизм кости [4,13]. Наши данные подтверждают связь низкой концентрации в сыворотке крови склеростина с частотой кальцификации сердца и сосудов.…”

Section: Discussionunclassified

Role of the morphogenetic proteins FGF-23 and Klotho and the glycoprotein sclerostin in the assessment of the risk of cardiovascular diseases and the prognosis of chronic kidney disease

Ly¹,

Ys²,

Dv³

et al. 2015

Ter. arkh.

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High phosphorus diet induces vascular calcification, a related decrease in bone mass and changes in the aortic gene expression

Cited by 139 publications

References 49 publications

Chondrocyte Rather Than Osteoblast Conversion of Vascular Cells Underlies Medial Calcification in Uremic Rats

Chondrocyte Rather Than Osteoblast Conversion of Vascular Cells Underlies Medial Calcification in Uremic Rats

MicroRNAs 29b, 133b, and 211 Regulate Vascular Smooth Muscle Calcification Mediated by High Phosphorus

Role of the morphogenetic proteins FGF-23 and Klotho and the glycoprotein sclerostin in the assessment of the risk of cardiovascular diseases and the prognosis of chronic kidney disease

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