Neuropathy and the vascular-bone axis in diabetes: Lessons from Charcot osteoarthropathy

Osteoporosis International

Volumn 25, Issue 4, 2014, Pages 1197-1207

  Petrova, N L ^a   Shanahan, C M ^b  

^a KING S COLLEGE HOSPITAL   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Bone fracture; Charcot osteoarthropathy; Diabetes; Neuropathy; RANKL OPG; Vascular calcification

Indexed keywords

ACID PHOSPHATASE TARTRATE RESISTANT ISOENZYME; ACUTE PHASE PROTEIN; ADVANCED GLYCATION END PRODUCT; ADVANCED GLYCATION END PRODUCT RECEPTOR; AMYLOID A PROTEIN; BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 4; C REACTIVE PROTEIN; CALCITONIN GENE RELATED PEPTIDE; CATHEPSIN K; COLONY STIMULATING FACTOR 1; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FIBRINOGEN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 6; LIGAND; NEUROPEPTIDE; OSTEOCALCIN; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; PLASMINOGEN ACTIVATOR INHIBITOR; STAT3 PROTEIN; TELOPEPTIDE; TRANSCRIPTION FACTOR MSX2; TRANSCRIPTION FACTOR RUNX2; TUMOR NECROSIS FACTOR ALPHA; AUTACOID; TNFSF11 PROTEIN, HUMAN;

BLOOD VESSEL CALCIFICATION; BONE DESTRUCTION; BONE DEVELOPMENT; BONE MINERALIZATION; CELL DIFFERENTIATION; CHARCOT OSTEOARTHROPATHY; DIABETES MELLITUS; DIABETIC NEUROPATHY; DISEASE ASSOCIATION; HUMAN; HYPERGLYCEMIA; INFLAMMATION; LIPID PEROXIDATION; NEUROPATHIC JOINT DISEASE; NONHUMAN; OSTEOARTHROPATHY; OSTEOLYSIS; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN GLYCOSYLATION; REVIEW; SIGNAL TRANSDUCTION; VASCULAR SMOOTH MUSCLE; ARTHROPATHY, NEUROGENIC; COMPLICATION; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY; VASCULAR CALCIFICATION;

ARTHROPATHY, NEUROGENIC; DIABETIC NEUROPATHIES; HUMANS; INFLAMMATION MEDIATORS; MUSCLE, SMOOTH, VASCULAR; OXIDATIVE STRESS; RANK LIGAND; SIGNAL TRANSDUCTION; VASCULAR CALCIFICATION;

EID: 84897876113     PISSN: 0937941X     EISSN: 14332965     Source Type: Journal    
DOI: 10.1007/s00198-013-2511-6     Document Type: Review

References (101)

1. Proudfoot D, Shanahan CM (2001) Biology of calcification in vascular cells: intima versus media. Herz 26:245-251 (Pubitemid 32612692)
2. London GM (2011) Arterial calcification: cardiovascular function and clinical outcome. Nefrologia 31:644-647
3. Maldonado N, Kelly-Arnold A, Vengrenyuk Y, Laudier D, Fallon JT, Virmani R, Cardoso L, Weinbaum S (2012) A mechanistic analysis of the role of microcalcifications in atherosclerotic plaque stability: potential implications for plaque rupture. Am J Physiol Heart Circ Physiol 303:H619-H628
4. Iyemere VP, Proudfoot D, Weissberg PL, Shanahan CM (2006) Vascular smooth muscle cell phenotypic plasticity and the regulation of vascular calcification. J Intern Med 260:192-210 (Pubitemid 44253633)
5. Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM (2011) Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 109:697-711
6. Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM (2003) Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol 23:489-494 (Pubitemid 36337227)
7. Villa-Bellosta R, Wang X, Millan JL, Dubyak GR, O'Neill WC (2011) Extracellular pyrophosphate metabolism and calcification in vascular smooth muscle. Am J Physiol Heart Circ Physiol 301:H61-H68
8. Kapustin AN, Davies JD, Reynolds JL et al (2011) Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization. Circ Res 109:e1-e12
9. Moon J-S, Clark VM, Beabout JW, Swee RG, Dyck PJ (2011) A controlled study of medial arterial calcification of legs: implications for diabetic polyneuropathy. Arch Neurol 68:1290-1294
10. Everhart JE, Pettitt DJ, KnowlerWC, Rose FA, Bennett PH (1988) Medial arterial calcification and its association with mortality and complications of diabetes. Diabetologia 31:16-23 (Pubitemid 18077567)
11. Singh DK, Winocour P, Summerhayes B, Kaniyur S, Viljoen A, Sivakumar G, Farrington K (2012) Prevalence and progression of peripheral vascular calcification in type 2 diabetes subjects with preserved kidney function. Diabetes Res Clin Pract 97:158-165
12. Lehto S, Niskanen L, Suhonen M, Ronnemaa T, Laakso M (1996) Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 16:978-983 (Pubitemid 26266896)
13. Niskanen L, Siitonen O, Suhonen M, Uusitupa MI (1994) Medial artery calcification predicts cardiovascularmortality in patients with NIDDM. Diabetes Care 17:1252-1256 (Pubitemid 24324967)
14. Mehrotra R, BudoffM, Christenson P, Ipp E, Takasu J, Gupta A, Norris K, Adler S (2004) Determinants of coronary artery calcification in diabetics with and without nephropathy. Kidney Int 66:2022-2031
15. Hamann C, Kirschner S, Gunther K-P, Hofbauer LC (2012) Bone, sweet bone-osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol 8:297-305
16. Bandeira E, Neves AP, Costa C, Bandeira F (2012) Association between vascular calcification and osteoporosis in men with type 2 diabetes. J Clin Densitom 15:55-60
17. Jeffcoate WJ, Rasmussen LM, Hofbauer LC, Game FL (2009) Medial arterial calcification in diabetes and its relationship to neuropathy. Diabetologia 52:2478-2488
18. Jeffcoate W (2004) Vascular calcification and osteolysis in diabetic neuropathy-is RANK-L the missing link? Diabetologia 47:1488-1492
19. Shanahan CM, Cary NRB, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME (1999) Medial localization of mineralizationregulating proteins in association with Monckeberg's sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 100:2168-2176
20. Liu Y, Shanahan CM (2011) Signalling pathways and vascular calcification. Front Biosci 16:1302-1314
21. Marra G, Cotroneo P, Pitocco D,Manto A, Di LeoMAS, RuotoloV, Caputo S, Giardina B, Ghirlanda G, Santini SA (2002) Early increase of oxidative stress and reduced antioxidant defenses in patients with uncomplicated type 1 diabetes: a case for gender difference. Diabetes Care 25:370-375 (Pubitemid 41079638)
22. Lopes-VirellaMF, Baker NL,Hunt KJ, Lachin J, NathanD,Virella G, Group DER (2011) Oxidized LDL immune complexes and coronary artery calcification in type 1 diabetes. Atherosclerosis 214:462-467
23. Brown AJ, Jessup W (1999) Oxysterols and atherosclerosis. Atherosclerosis 142:1-28 (Pubitemid 28553934)
24. Liu H, Yuan L, Xu S, Zhang T, Wang K (2004) Cholestane-3beta, 5alpha, 6beta-triol promotes vascular smooth muscle cells calcification. Life Sci 76:533-543 (Pubitemid 39535665)
25. Byon CH, Javed A, Dai Q, Kappes JC, Clemens TL, Darley-Usmar VM, McDonald JM, Chen Y (2008) Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor runx2 by AKTsignaling. J Biol Chem 283:15319-15327
26. Node K, Inoue T (2009) Postprandial hyperglycemia as an etiological factor in vascular failure. Cardiovasc 8:23
27. Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11:98-107
28. Alman AC, Kinney GL, Tracy RP, Maahs DM, Hokansen JE, Rewere MJ, Snell-Bergeon JK (2013) Prospective association between inflammatory markers and progression of coronary artery calcification in adults with and without type1 diabetes. Diabetes Care 36(7):1967-1973
29. Thomsen SB, Rathcke CN, Zerahn B, Vestergaard H (2010) Increased levels of the calcification marker matrix gla protein and the inflammatory markers YKL-40 and CRP in patients with type 2 diabetes and ischemic heart disease. Cardiovasc 9:86
30. Satoh J, Yagihashi S, Toyota T (2003) The possible role of tumor necrosis factor-alpha in diabetic polyneuropathy. Exp Diabesity Res 4:65-71 (Pubitemid 37080774)
31. La Fontaine J, Harkless LB, Sylvia VL, Carnes D, Heim-Hall J, Jude E (2008) Levels of endothelial nitric oxide synthase and calcitonin gene-related peptide in the Charcot foot: a pilot study. J Foot Ankle Surg 47:424-429
32. Thompson B, Towler DA (2012) Arterial calcification and bone physiology: role of the bone-vascular axis. Nat Rev Endocrinol 8: 529-543
33. AbedinM, Lim J, Tang TB, Park D,Demer LL, TintutY (2006) N-3 fatty acids inhibit vascular calcification via the p38-mitogen-activated protein kinase and peroxisome proliferator-activated receptor-gamma pathways. Circ Res 98:727-729
34. Shao J-S, Cheng S-L, Sadhu J, TowlerDA (2010) Inflammation and the osteogenic regulation of vascular calcification: a review and perspective. Hypertension 55:579-592
35. Lutgers HL, Graaff R, Links TP, Ubink-Veltmaat LJ, Bilo HJ, Gans RO, Smit AJ (2006) Skin autofluorescence as a noninvasive marker of vascular damage in patients with type 2 diabetes. Diabetes Care 29:2654-2659 (Pubitemid 44912194)
36. Li S-l, ReddyMA, Cai Q,Meng L, Yuan H, Lanting L, Natarajan R (2006) Enhanced proatherogenic responses in macrophages and vascular smooth muscle cells derived from diabetic db/db mice. Diabetes 55:2611-2619 (Pubitemid 44871163)
37. Soro-Paavonen A, Watson AMD, Li J et al (2008) Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in diabetes. Diabetes 57:2461-2469
38. Wang Z, Jiang Y, Liu N, Ren L, Zhu Y, An Y, Chen D (2012) Advanced glycation end-product N -carboxymethyl-lysine accelerates progression of atherosclerotic calcification in diabetes. Atherosclerosis 221:387-396
39. Suga T, Iso T, Shimizu T, Tanaka T, Yamagishi S-i, Takeuchi M, Imaizumi T, Kurabayashi M (2011) Activation of receptor for advanced glycation end products induces osteogenic differentiation of vascular smooth muscle cells. J Atheroscler Thromb 18:670-683
40. Tesfaye S, Boulton AJM, Dyck PJ et al (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33:2285-2293
41. Edmonds ME, Morrison N, Laws JW, Watkins PJ (1982) Medial arterial calcification and diabetic neuropathy. Br Med J (Clin Res Ed) 284:928-930 (Pubitemid 12192941)
42. Shanahan CM (2007) Inflammation ushers in calcification: a cycle of damage and protection? Circulation 116:2782-2785
43. Vincent AM, Russell JW, Low P, Feldman EL (2004) Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev 25:612-628 (Pubitemid 39096072)
44. Yorek MA (2003) The role of oxidative stress in diabetic vascular and neural disease. Free Radic Res 37:471-480 (Pubitemid 36410886)
45. Huijberts MSP, Schaper NC, Schalkwijk CG (2008) Advanced glycation end products and diabetic foot disease. Diabetes Metab Res Rev 24(Suppl 1):S19-S24 (Pubitemid 351802767)
46. Figueroa-Romero C, Sadidi M, Feldman EL (2008)Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord 9:301-314
47. Herder C, Lankisch M, Ziegler D et al (2009) Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA survey F3 (Augsburg, Germany). Diabetes Care 32:680-682
48. Yamakawa I, Kojima H, Terashima T et al (2011) Inactivation of TNF-α ameliorates diabetic neuropathy in mice. Am J Physiol Endocrinol Metab 301:E844-E852
49. Meerwaldt R, Links TP, Graaff R, Hoogenberg K, Lefrandt JD, Baynes JW, Gans ROB, Smit AJ (2005) Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy. Diabetologia 48:1637-1644 (Pubitemid 41175518)
50. Vlassara H, Brownlee M, Cerami A (1981) Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus. Proc Natl Acad Sci U S A 78:5190-5192 (Pubitemid 12229699)
51. Toth C, Rong LL, Yang C et al (2008) Receptor for advanced glycation end products (RAGEs) and experimental diabetic neuropathy. Diabetes 57:1002-1017
52. Hak AE, Pols HA, van Hemert AM, Hofman A, Witteman JC (2000) Progression of aortic calcification is associated with metacarpal bone loss duringmenopause: a population-based longitudinal study. Arterioscler Thromb Vasc Biol 20:1926-1931 (Pubitemid 30644642)
53. Kado DM, Browner WS, Blackwell T, Gore R, Cummings SR (2000) Rate of bone loss is associated with mortality in older women: a prospective study. J Bone Miner Res 15:1974-1980
54. den Uyl D, Nurmohamed MT, van Tuyl LH, Raterman HG, Lems WF (2011) (Sub)clinical cardiovascular disease is associated with increased bone loss and fracture risk; a systematic review of the association between cardiovascular disease and osteoporosis. Arthritis Res Ther 13(1):R5
55. Young MJ, Marshall A, Adams JE, Selby PL, Boulton AJ (1995) Osteopenia, neurological dysfunction, and the development of Charcot neuroarthropathy. Diabetes Care 18:34-38
56. Rix M, Andreassen H, Eskildsen P (1999) Impact of peripheral neuropathy on bone density in patients with type 1 diabetes. Diabetes Care 22:827-831 (Pubitemid 29220788)
57. Schoppet M, Preissner KT, Hofbauer LC (2002) RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol 22:549-553 (Pubitemid 34408732)
58. Collin-Osdoby P (2004) Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res 95:1046-1057
59. Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473:139-146
60. Bucay N, Sarosi I, Dunstan CR et al (1998) Osteoprotegerindeficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12:1260-1268 (Pubitemid 28213402)
61. Simonet WS, Lacey DL, Dunstan CR et al (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309-319 (Pubitemid 27199902)
62. Min H, Morony S, Sarosi I et al (2000) Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J Exp Med 192:463-474 (Pubitemid 30666247)
63. Dhore CR, Cleutjens JP, Lutgens E, Cleutjens KB, Geusens PP, Kitslaar PJ, Tordoir JH, Spronk HM, Vermeer C, Daemen MJ (2001) Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 21:1998-2003 (Pubitemid 34219753)
64. Panizo S, Cardus A, Encinas M, Parisi E, Valcheva P, Lopez-Ongil S, Coll B, Fernandez E, Valdivielso JM (2009) RANKL increases vascular smooth muscle cell calcification through a RANK-BMP4-dependent pathway. Circ Res 104:1041-1048
65. Schoppet M, Kavurma MM, Hofbauer LC, Shanahan CM (2011) Crystallizing nanoparticles derived from vascular smooth muscle cells contain the calcification inhibitor osteoprotegerin. Biochem Biophys Res Commun 407:103-107
66. Browner WS, Lui LY, Cummings SR (2001) Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, andmortality in elderly women. J Clin Endocrinol Metab 86:631-637 (Pubitemid 32207471)
67. Anand DV, Lahiri A, Lim E, Hopkins D, Corder R (2006) The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. J Am Coll Cardiol 47:1850-1857
68. Reinhard H, Lajer M, Gall M-A, Tarnow L, Parving H-H, Rasmussen LM, Rossing P (2010) Osteoprotegerin and mortality in type 2 diabetic patients. Diabetes Care 33:2561-2566
69. Aoki A, Murata M, Asano T et al (2013) Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes. Cardiovasc 12:11
70. Pittenger G, Vinik A (2003) Nerve growth factor and diabetic neuropathy. Exp Diabesity Res 4:271-285 (Pubitemid 38035567)
71. Bjurholm A, Kreicbergs A, Schultzberg M, Lerner UH (1992) Neuroendocrine regulation of cyclic AMP formation in osteoblastic cell lines (UMR-106-01, ROS 17/2.8,MC3T3-E1, and Saos-2) and primary bone cells. J Bone Miner Res 7:1011-1019
72. Bernard GW, Shih C (1990) The osteogenic stimulating effect of neuroactive calcitonin gene-related peptide. Peptides 11:625-632 (Pubitemid 20289029)
73. Santavirta S, Konttinen YT, Nordstrom D, Makela A, Sorsa T, Hukkanen M, Rokkanen P (1992) Immunologic studies of nonunited fractures. Acta Orthop Scand 63:579-586 (Pubitemid 23012661)
74. Wang L, Shi X, Zhao R, Halloran BP, Clark DJ, Jacobs CR, Kingery WS (2010) Calcitonin-gene-related peptide stimulates stromal cell osteogenic differentiation and inhibits RANKL induced NF-kappaB activation, osteoclastogenesis and bone resorption. Bone 46:1369-1379
75. Connat JL, Busseuil D, Gambert S et al (2001) Modification of the rat aortic wall during ageing; possible relation with decrease of peptidergic innervation. Anat Embryol (Berl) 204:455-468 (Pubitemid 34143492)
76. Sharma A, Scammell BE, Fairbairn KJ, Seagrave MJ, Game FL, JeffcoateWJ (2010) Prevalence of calcification in the pedal arteries in diabetes complicated by foot disease. Diabetes Care 33:e66
77. Petrova NL, Edmonds ME (2008) Charcot neuroosteoarthropathy-current standards. Diabetes Metab Res Rev 24(Suppl 1):S58-S61
78. Sinha S, Munichoodappa CS, Kozak GP (1972) Neuro-arthropathy (Charcot joints) in diabetes mellitus (clinical study of 101 cases). Medicine (Baltimore) 51:191-210
79. Cavanagh PR, Young MJ, Adams JE, Vickers KL, Boulton AJ (1994) Radiographic abnormalities in the feet of patients with diabetic neuropathy. Diabetes Care 17:201-209 (Pubitemid 24065517)
80. SinacoreDR,WithringtonNC (1999)Recognition andmanagement of acute neuropathic (Charcot) arthropathies of the foot and ankle. J Orthop Sports Phys Ther 29:736-746
81. van Baal J, Hubbard R, Game F, Jeffcoate W (2010) Mortality associated with acute Charcot foot and neuropathic foot ulceration. Diabetes Care 33:1086-1089
82. Gazis A, Pound N, Macfarlane R, Treece K, Game F, Jeffcoate W (2004) Mortality in patients with diabetic neuropathic osteoarthropathy (Charcot foot). Diabet Med 21:1243-1246 (Pubitemid 39472381)
83. EdmondsMEKBA, Saldana Chaparro R,Dew T, Stock S,Moniz C, Petrova NL (2009) Serum levels of osteoprotegerin are raised in diabetic peripheral neuropathy and are significantly correlated with peripheral arterial calcification. Diabetologia 52:S97
84. Ndip A, Williams A, Jude EB, Serracino-Inglott F, Richardson S, Smyth JV, Boulton AJM, Alexander MY (2011) The RANKL/RANK/OPG signaling pathway mediates medial arterial calcification in diabetic Charcot neuroarthropathy. Diabetes 60:2187-2196
85. Mabilleau G, Petrova NL, Edmonds ME, Sabokbar A (2008) Increased osteoclastic activity in acute Charcot's osteoarthropathy: the role of receptor activator of nuclear factor-kappaB ligand. Diabetologia 51:1035-1040
86. Alexander MY (2009) RANKL links arterial calcification with osteolysis. Circ Res 104:1032-1034
87. Stevens MJ, EdmondsME, Foster AV,Watkins PJ (1992) Selective neuropathy and preserved vascular responses in the diabetic Charcot foot. Diabetologia 35:148-154
88. Rogers LC, Frykberg RG, Armstrong DG et al (2011) The Charcot foot in diabetes. Diabetes Care 34:2123-2129
89. Edmonds M, Dew T,Musto R, Thomson S, Sherwood R,Moniz C, Petrova NL (2008) Serum proinflammatory cytokines TNF-alpha and IL-6 are raised in acute Charcot osteoarthropathy and correlate with a marker of bone resorption. Diabetologia 51(Suppl 1):S510
90. Petrova NL, Foster AVM, Edmonds ME (2005) Calcaneal bone mineral density in patients with Charcot neuropathic osteoarthropathy: differences between type 1 and type 2 diabetes. Diabet Med 22:756-761 (Pubitemid 40805898)
91. Petrova NL, Edmonds ME (2010) A prospective study of calcaneal bone mineral density in acute Charcot osteoarthropathy. Diabetes Care 33:2254-2256
92. Petrova NL, Shanahan C, EdmondsM(2011) The proinflammatory cytokines TNF-α and IL-6 modulate RANKL-mediated osteoclastic resorption in vitro in patients with acute Charcot osteoarthropathy. Diabetologia 54(Suppl 1):S11
93. Lam J, Takeshita S, Barker JE, Kanagawa O, Ross FP, Teitelbaum SL (2000) TNF-alpha induces osteoclastogenesis by direct stimulation of macrophages exposed to permissive levels of RANK ligand. J Clin Investig 106:1481-1488 (Pubitemid 32038586)
94. Baumhauer JF, O'Keefe RJ, Schon LC, Pinzur MS (2006) Cytokine-induced osteoclastic bone resorption in charcot arthropathy: an immunohistochemical study. Foot Ankle Int 27:797-800
95. Al-Aly Z (2007) Medial vascular calcification in diabetes mellitus and chronic kidney disease: the role of inflammation. Cardiovasc Hematol Disord Drug Targets 7:1-6
96. Jeffcoate WJ, Game F, Cavanagh PR (2005) The role of proinflammatory cytokines in the cause of neuropathic osteoarthropathy (acute Charcot foot) in diabetes. Lancet 366:2058-2061 (Pubitemid 41773381)
97. Sun YBC, Yuan K, Chen J, Mao X, Heath JM, Javed A, Zhang K, Anderson PG, Chen Y (2012) Smooth muscle cell-specific runx2 deficiency inhibits vascular calcification. Circ Res 111:543-552
98. Byon CH, Sun Y, Chen J et al (2011) Runx2-upregulated receptor activator of nuclear factor kB ligand in calcifying smooth muscle cells promotes migration and osteoclastic differentiation of macrophages. Arterioscler Thromb Vasc Biol 31:1387-1396
99. Mabilleau G, Petrova N, EdmondsME, Sabokbar A (2011) Number of circulating CD14-positive cells and the serum levels of TNF-α are raised in acute charcot foot. Diabetes Care 34:e33
100. Kon T, Cho TJ, Aizawa T, Yamazaki M, Nooh N, Graves D, Gerstenfeld LC, Einhorn TA (2001) Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. J Bone Miner Res 16:1004-1014 (Pubitemid 32467144)
101. Petrova NL, Edmonds M (2013) Medical management of Charcot arthropathy. Diab Obes Met 15:193-197