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Calcified Tissue International

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29.07.2016 | Original Research

Calcium Phosphate Crystals from Uremic Serum Promote Osteogenic Differentiation in Human Aortic Smooth Muscle Cells

verfasst von: Yaorong Liu, Lin Zhang, Zhaohui Ni, Jiaqi Qian, Wei Fang

Erschienen in: Calcified Tissue International | Ausgabe 5/2016

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Abstract

Recent study demonstrated that calcium phosphate (CaP) crystals isolated from high phosphate medium were a key contributor to arterial calcification. The present study further investigated the effects of CaP crystals induced by uremic serum on calcification of human aortic smooth muscle cells. This may provide a new insight for the development of uremic cardiovascular calcification. We tested the effects of uremic serum or normal serum on cell calcification. Calcification was visualized by staining and calcium deposition quantified. Expression of various bone-calcifying genes was detected by real-time PCR, and protein levels were quantified by western blotting or enzyme-linked immunosorbent assays. Pyrophosphate was used to investigate the effects of CaP crystals’ inhibition. Finally, CaP crystals were separated from uremic serum to determine its specific pro-calcification effects. Uremic serum incubation resulted in progressively increased calcification staining and increased calcium deposition in HASMCs after 4, 8 and 12 days (P vs 0 day <0.001 for all). Compared to cells incubated in control serum, uremic serum significantly induced the mRNA expression of bone morphogenetic factor-2, osteopontin and RUNX2, and increased their protein levels as well (P < 0.05 for all). Inhibition of CaP crystals with pyrophosphate incubation prevented calcium deposition and bone-calcifying gene over-expression increased by uremic serum. CaP crystals, rather than the rest of uremic serum, were responsible for these effects. Uremic serum accelerates arterial calcification by mediating osteogenic differentiation. This effect might be mainly attributed to the CaP crystal content.

Levey AS, Beto JA, Coronado BE, Eknoyan G, Foley RN, Kasiske BL, Klag MJ, Mailloux LU, Manske CL, Meyer KB, Parfrey PS, Pfeffer MA, Wenger NK, Wilson PW, Wright JT (1998) Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis 32:853–906CrossRefPubMed

Wheeler DC (1996) Cardiovascular disease in patients with chronic renal failure. Lancet 348:1673–1674CrossRefPubMed

Schlieper G, Kruger T, Djuric Z, Damjanovic T, Markovic N, Schurgers LJ, Brandenburg VM, Westenfeld R, Dimkovic S, Ketteler M, Grootendorst DC, Dekker FW, Floege J, Dimkovic N (2008) Vascular access calcification predicts mortality in hemodialysis patients. Kidney Int 74:1582–1587CrossRefPubMed

Guérin AP, London GM, Marchais SJ, Metivier F (2000) Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 15:1014–1021CrossRefPubMed

Wu M, Rementer C, Giachelli CM (2013) Vascular calcification: an update on mechanisms and challenges in treatment. Calcif Tissue Int 93:365–373CrossRefPubMedPubMedCentral

Schlieper G, Aretz A, Verberckmoes SC, Kruger T, Behets GJ, Ghadimi R, Weirich TE, Rohrmann D, Langer S, Tordoir JH, Amann K, Westenfeld R, Brandenburg VM, D’Haese PC, Mayer J, Ketteler M, McKee MD, Floege J (2010) Ultrastructural analysis of vascular calcifications in uremia. J Am Soc Nephrol 21:689–696CrossRefPubMedPubMedCentral

Ewence AE, Bootman M, Roderick HL, Skepper JN, McCarthy G, Epple M, Neumann M, Shanahan CM, Proudfoot D (2008) Calcium phosphate crystals induce cell death in human vascular smooth muscle cells: a potential mechanism in atherosclerotic plaque destabilization. Circ Res 103:e28–e34CrossRefPubMed

Nadra I, Mason JC, Philippidis P, Florey O, Smythe CD, McCarthy GM, Landis RC, Haskard DO (2005) Proinflammatory activation of macrophages by basic calcium phosphate crystals via protein kinase C and MAP kinase pathways: a vicious cycle of inflammation and arterial classification? Circ Res 96:1248–1256CrossRefPubMed

Major ML, Cheung HS, Misra RP (2007) Basic calcium phosphate crystals activate c-fos expression through a Ras/ERK dependent signaling mechanism. Biochem Biophys Res Commun 355:654–660CrossRefPubMedPubMedCentral

10.

Sun Y, Zeng XR, Wenger L, Cheung HS (2003) Basic calcium phosphate crystals stimulate the endocytotic activity of cells—inhibition by anti-calcification agents. Biochem Biophys Res Commun 312:1053–1059CrossRefPubMed

11.

Villa-Bellosta R, Millan A, Sorribas V (2010) Role of calcium-phosphate deposition in vascular smooth muscle cell calcification. AJP Cell Physiol 300:C210–C220CrossRef

12.

Sage AP, Lu J, Tintut Y, Demer LL (2011) Hyperphosphatemia-induced nanocrystals upregulate the expression of bone morphogenetic protein-2 and osteopontin genes in mouse smooth muscle cells in vitro. Kidney Int 79:414–422CrossRefPubMed

13.

Chen NX, Duan D, O’Neill KD, Wolisi GO, Koczman JJ, Laclair R, Moe SM (2006) The mechanisms of uremic serum-induced expression of bone matrix proteins in bovine vascular smooth muscle cells. Kidney Int 70:1046–1053CrossRefPubMed

14.

Young JD, Martel J, Young D, Young A, Hung CM, Young L, Chao YJ, Young J, Wu CY (2009) Characterization of granulations of calcium and apatite in serum as pleomorphic mineralo-protein complexes and as precursors of putative nanobacteria. PLoS One 4:e5421CrossRefPubMedPubMedCentral

15.

Young JD, Martel J, Young L, Wu CY, Young A, Young D (2009) Putative nanobacteria represent physiological remnants and culture by-products of normal calcium homeostasis. PLoS One 4:e4417CrossRefPubMedPubMedCentral

16.

Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL (1993) Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest 91:1800–1809CrossRefPubMedPubMedCentral

17.

Moe SM, Duan D, Doehle BP, O’Neill KD, Chen NX (2003) Uremia induces the osteoblast differentiation factor Cbfa1 in human blood vessels. Kidney Int 63:1003–1011CrossRefPubMed

18.

Byon CH, Chen Y (2015) Molecular mechanisms of vascular calcification in chronic kidney disease: the link between bone and the vasculature. Curr Osteoporos Rep 13:206–215CrossRefPubMedPubMedCentral

19.

Rong S, Zhao X, Jin X, Zhang Z, Chen L, Zhu Y, Yuan W (2014) Vascular calcification in chronic kidney disease is induced by bone morphogenetic protein-2 via a mechanism involving the Wnt/beta-catenin pathway. Cell Physiol Biochem 34:2049–2060CrossRefPubMed

20.

Wada T, McKee MD, Steitz S, Giachelli CM (1999) Calcification of vascular smooth muscle cell cultures: inhibition by osteopontin. Circ Res 84:166–178CrossRefPubMed

21.

Jono S, Peinado C, Giachelli CM (2000) Phosphorylation of osteopontin is required for inhibition of vascular smooth muscle cell calcification. J Biol Chem 275:20197–20203CrossRefPubMed

22.

Bostrom KI, Rajamannan NM, Towler DA (2011) The regulation of valvular and vascular sclerosis by osteogenic morphogens. Circ Res 109:564–577CrossRefPubMedPubMedCentral

23.

Harmey D, Hessle L, Narisawa S, Johnson KA, Terkeltaub R, Millán JL (2004) Concerted regulation of inorganic pyrophosphate and osteopontin by Akp2, Enpp1, and Ank. Am J Pathol 164:1199–1209CrossRefPubMedPubMedCentral

24.

Lomashvili KA, Cobbs S, Hennigar RA, Hardcastle KI, O’Neill WC (2004) Phosphate-induced vascular calcification: role of pyrophosphate and osteopontin. J Am Soc Nephrol 15:1392–1401CrossRefPubMed

25.

Lomashvili KA, Garg P, Narisawa S, Millan JL, O’Neill WC (2008) Upregulation of alkaline phosphatase and pyrophosphate hydrolysis: potential mechanism for uremic vascular calcification. Kidney Int 73:1024–1030CrossRefPubMedPubMedCentral

26.

Addison WN, Azari F, Sorensen ES, Kaartinen MT, McKee MD (2007) Pyrophosphate inhibits mineralization of osteoblast cultures by binding to mineral, up-regulating osteopontin, and inhibiting alkaline phosphatase activity. J Biol Chem 282:15872–15883CrossRefPubMed

27.

Terkeltaub R (2006) Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcification. Purinergic Signal 2:371–377CrossRefPubMedPubMedCentral

28.

O’Neill WC, Sigrist MK, McIntyre CW (2010) Plasma pyrophosphate and vascular calcification in chronic kidney disease. Nephrol Dial Transpl 25:187–191CrossRef

29.

Meyer JL (1984) Can biological calcification occur in the presence of pyrophosphate? Arch Biochem Biophys 231:1–8CrossRefPubMed

30.

Russell RG, Bisaz S, Fleisch H (1969) Pyrophosphate and diphosphonates in calcium metabolism and their possible role in renal failure. Arch Intern Med 124:571–577CrossRefPubMed

31.

Francis MD, Russell RG, Fleisch H (1969) Diphosphonates inhibit formation of calcium phosphate crystals in vitro and pathological calcification in vivo. Science (New York, NY) 165:1264–1266CrossRef

32.

Louvet L, Bazin D, Büchel J, Steppan S, Passlick-Deetjen J, Massy ZA (2015) Characterisation of calcium phosphate crystals on calcified human aortic vascular smooth muscle cells and potential role of magnesium. PLoS One 10:e0115342CrossRefPubMedPubMedCentral

33.

Jia Z, Wang S, Tang J, He D, Cui L, Liu Z, Guo B, Huang L, Lu Y, Hu H (2014) Does crystal deposition in genetic hypercalciuric rat kidney tissue share similarities with bone formation? Urology 83(509):e7–e14PubMed

34.

Sohnel O, Grases F (2011) Supersaturation of body fluids, plasma and urine, with respect to biological hydroxyapatite. Urol Res 39:429–436CrossRefPubMed

35.

O’Neill WC (2007) The fallacy of the calcium–phosphorus product. Kidney Int 72:792–796CrossRefPubMed

36.

Blumenthal NC (1989) Mechanisms of inhibition of calcification. Clin Orthop Relat Res 247: 279–289PubMed

37.

Price PA, Nguyen TM, Williamson MK (2003) Biochemical characterization of the serum fetuin-mineral complex. J Biol Chem 278:22153–22160CrossRefPubMed

38.

Villa-Bellosta R, Sorribas V (2011) Calcium phosphate deposition with normal phosphate concentration. -Role of pyrophosphate-. Circ J 75:2705–2710CrossRefPubMed

39.

Heiss A, Eckert T, Aretz A, Richtering W, van Dorp W, Schafer C, Jahnen-Dechent W (2008) Hierarchical role of fetuin-A and acidic serum proteins in the formation and stabilization of calcium phosphate particles. J Biol Chem 283:14815–14825CrossRefPubMed

40.

Heiss A, DuChesne A, Denecke B, Grotzinger J, Yamamoto K, Renne T, Jahnen-Dechent W (2003) Structural basis of calcification inhibition by alpha 2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem 278:13333–13341CrossRefPubMed

41.

Herrmann M, Schafer C, Heiss A, Graber S, Kinkeldey A, Buscher A, Schmitt MM, Bornemann J, Nimmerjahn F, Herrmann M, Helming L, Gordon S, Jahnen-Dechent W (2012) Clearance of fetuin-A—containing calciprotein particles is mediated by scavenger receptor-A. Circ Res 111:575–584CrossRefPubMed

42.

Heiss A, Jahnen-Dechent W, Endo H, Schwahn D (2007) Structural dynamics of a colloidal protein-mineral complex bestowing on calcium phosphate a high solubility in biological fluids. Biointerphases 2:16–20CrossRefPubMed

43.

Wang AY, Woo J, Lam CW, Wang M, Chan IH, Gao P, Lui SF, Li PK, Sanderson JE (2005) Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transpl 20:1676–1685CrossRef

44.

Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Bohm R, Metzger T, Wanner C, Jahnen-Dechent W, Floege J (2003) Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 361:827–833CrossRefPubMed

45.

Stenvinkel P, Wang K, Qureshi AR, Axelsson J, Pecoits-Filho R, Gao P, Barany P, Lindholm B, Jogestrand T, Heimburger O, Holmes C, Schalling M, Nordfors L (2005) Low fetuin-A levels are associated with cardiovascular death: impact of variations in the gene encoding fetuin. Kidney Int 67:2383–2392CrossRefPubMed

46.

Moe SM, Reslerova M, Ketteler M, O’Neill K, Duan D, Koczman J, Westenfeld R, Jahnen-Dechent W, Chen NX (2005) Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int 67:2295–2304CrossRefPubMed

47.

Pateinakis P, Papagianni A, Douma S, Efstratiadis G, Memmos D (2013) Associations of fetuin-A and osteoprotegerin with arterial stiffness and early atherosclerosis in chronic hemodialysis patients. BMC Nephrol 14:122CrossRefPubMedPubMedCentral

48.

Hermans MM, Brandenburg V, Ketteler M, Kooman JP, van der Sande FM, Boeschoten EW, Leunissen KM, Krediet RT, Dekker FW (2007) Association of serum fetuin-A levels with mortality in dialysis patients. Kidney Int 72:202–207CrossRefPubMed

49.

Reynolds JL, Skepper JN, McNair R, Kasama T, Gupta K, Weissberg PL, Jahnen-Dechent W, Shanahan CM (2005) Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. J Am Soc Nephrol 16:2920–2930CrossRefPubMed

50.

Price PA, Lim JE (2003) The inhibition of calcium phosphate precipitation by fetuin is accompanied by the formation of a fetuin-mineral complex. J Biol Chem 278:22144–22152CrossRefPubMed

51.

Matsui I, Hamano T, Mikami S, Fujii N, Takabatake Y, Nagasawa Y, Kawada N, Ito T, Rakugi H, Imai E, Isaka Y (2009) Fully phosphorylated fetuin-A forms a mineral complex in the serum of rats with adenine-induced renal failure. Kidney Int 75:915–928CrossRefPubMed

52.

Proudfoot D, Shanahan CM (2011) Nanocrystals seed calcification in more ways than one. Kidney Int 79:379–382CrossRefPubMed

53.

Nabiev I, Mitchell S, Davies A, Williams Y, Kelleher D, Moore R, Gun’ko YK, Byrne S, Rakovich YP, Donegan JF, Sukhanova A, Conroy J, Cottell D, Gaponik N, Rogach A, Volkov Y (2007) Nonfunctionalized nanocrystals can exploit a cell’s active transport machinery delivering them to specific nuclear and cytoplasmic compartments. Nano Lett 7:3452–3461CrossRefPubMed

Titel: Calcium Phosphate Crystals from Uremic Serum Promote Osteogenic Differentiation in Human Aortic Smooth Muscle Cells
verfasst von: Yaorong Liu
Lin Zhang
Zhaohui Ni
Jiaqi Qian
Wei Fang
Publikationsdatum: 29.07.2016
Verlag: Springer US
Erschienen in: Calcified Tissue International / Ausgabe 5/2016
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-016-0182-y

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