Is "fibrodysplasia ossificans progressiva" a vascular disease? A groundbreaking pathogenic model;¿Es la «fibrodisplasia osificante progresiva» una enfermedad de origen vascular? Un modelo patogénico innovador

Reumatologia Clinica

Volumn 10, Issue 6, 2014, Pages 389-395

  Morales Piga, Antonio ^a   Bachiller Corral, Francisco Javier ^b   Sánchez Duffhues, Gonzalo ^c  

^a CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE ENFERMEDADES RARAS CIBERER   (Spain)

^b HOSPITAL RAMÓN Y CAJAL   (Spain)

^c Departamento de Biología Molecular y Celular del Leids Universitair Medisch Centrum LUMC   (Spain)

Author keywords

Bone morphogenetic protein; Endothelial mesenchymal transition; Fibrodysplasia ossificans progressive; Mutation

Indexed keywords

DISEASE MODEL; HUMAN; OSSIFYING MYOSITIS; PATHOGENICITY; SHORT SURVEY; VASCULAR DISEASE; BIOLOGICAL MODEL; GENETIC MARKER; GENETIC PREDISPOSITION; MUTATION; MYOSITIS OSSIFICANS; PATHOPHYSIOLOGY; VASCULAR DISEASES;

GENETIC MARKER;

GENETIC MARKERS; GENETIC PREDISPOSITION TO DISEASE; HUMANS; MODELS, BIOLOGICAL; MUTATION; MYOSITIS OSSIFICANS; VASCULAR DISEASES;

EID: 84908324077     PISSN: 1699258X     EISSN: 18851398     Source Type: Journal    
DOI: 10.1016/j.reuma.2014.05.001     Document Type: Short Survey

References (104)

1. Pennsylvania Researchers Discover Gene That Causes Second Skeleton to form. News release 2006 [consultado 22 May 2014]. Disponible en: http://www.ifopa.org/penn-researchers-discover-gene-that-creates-second-skeleton.html.
2. Kaplan F.S., Chakkalakal S.A., Shore E.M. Fibrodysplasia ossificans progressiva: Mechanisms and models of skeletal metamorphosis. Dis Model Mech 2012, 5:756-762.
3. Morales-Piga A., Kaplan F.S. Osteochondral diseases and fibrodysplasia ossificans progressiva. Adv Exp Med Biol 2010, 686:335-348.
4. Rare diseases: understanding this Public Health Priority. Eurordis 2005 [consultado 22 May 2014]. Disponible en: http://www.eurordis.org/IMG/pdf/princeps_document-EN.pdf.
5. Connor J.M., Evans D.A.P. Genetic aspects of fibrodysplasia ossificans progressiva. J Med Genet 1982, 19:35-39.
6. Shore E.M., Feldman G.J., Xu M., Kaplan F.S. The Genetics of Fibrodysplasia Ossificans Progressiva. Clin Rev Bone Miner Metab 2005, 3:201-204.
7. Pignolo R.J., Shore E.M., Kaplan F.S. Fibrodysplasia ossificans progressiva: Clinical and genetic aspects. Orphanet J Rare Dis 2011, 6:80.
8. Zhang W., Zhang K., Song L., Pang J., Ma H., Shore E.M., et al. The phenotype and genotype of fibrodysplasia ossificans progressiva in China: A report of 72 cases. Bone 2013, 57:386-391.
9. Morales-Piga A., Bachiller-Corral J., Trujillo-Tiebas M.J., Villaverde-Hueso A., Gamir-Gamir M.L., Alonso-Ferreira V., et al. Fibrodysplasia ossificans progressiva in Spain: Epidemiological, clinical, and genetic aspects. Bone 2012, 51:748-755.
10. Rogers J.G., Chase G.A. Paternal age effect in fibrodysplasia ossificans progressiva. J Med Genet 1979, 16:147-148.
11. Kaplan F.S., Tabas J.A., Gannon F.H., Finkel G., Hahn G.V., Zasloff M.A. The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. JBJS 1993, 75:220-230.
12. Kaplan F.S., Le Merrer M., Glaser D.L., Pignolo R.J., Goldsby R.E., Kitterman J.A., et al. Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol 2008, 22:191-205.
13. Kartal-Kaess M., Shore E.M., Xu M., Schwering L., Uhl M., Korinthenberg R., et al. Fibrodysplasia ossificans progressiva (FOP): Watch the great toes!. Eur J Pediatr 2010, 169:1417-1421.
14. Nakashima Y., Haga N., Kitoh H., Kamizono J., Tozawa K., Katagiri T., et al. Deformity of the great toe in fibrodysplasia ossificans progressiva. J Orthop Sci 2010, 15:804-809.
15. Schroeder H.W., Zasloff M. The hand and foot malformations in fibrodysplasia ossificans progressiva. Johns Hopkins Med J 1980, 147:73-78.
16. Connor J.M., Smith R. The cervical spine in fibrodysplasia ossificans progressiva. Br J Radiol 1982, 55:492-496.
17. Shah P.B., Zasloff M.A., Drummond D., Kaplan F.S. Spinal deformity in patients who have fibrodysplasia ossificans progressiva. JBJS 1994, 76:1442-1450.
18. Schaffer A.A., Kaplan F.S., Tracy M.R., O'Brien M.L., Dormans J.P., Shore E.M., et al. Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome: Clues from the BMP signaling pathway. Spine 2005, 30:1379-1385.
19. Deirmengian G.K., Hebela N.M., O'Connell M., Glaser D.L., Shore E.M., Kaplan F.S. Proximal tibial osteochondromas in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am 2008, 90:366-374.
20. Kaplan F.S., Glaser D.L., Shore E.M., Deirmengian G.K., Gupta R., Delai P., et al. The phenotype of fibrodysplasia ossificans progressiva. Clin Rev Bone Miner Metab 2005, 3:183-188.
21. Cohen R.B., Hahn G.V., Tebas J.A., Peeper J., Levitz C.L., Sando A. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. J Bone Joint Surg Am 1993, 75:215-219.
22. Roush W. Protein builds second skeleton. Science 1996, 273:1170.
23. Pignolo R.J., Shore E.M., Kaplan F.S. Fibrodysplasia ossificans progressiva: Diagnosis, management, and therapeutic horizons. Pediatr Endocrinol Rev 2013, 10(Suppl 2):437-448.
24. Levy C.E., Lash A.T., Janoff H.B., Kaplan F.S. Conductive hearing loss in individuals with fibrodysplasia ossificans progressiva. Am J Audiol 1999, 8:29-33.
25. Kitterman J.A., Strober J.B., Kan L., Rocke D.M., Cali A., Peeper J., et al. Neurological symptoms in individuals with fibrodysplasia ossificans progressiva. J Neurol 2012, 259:2636-2643.
26. Kan L., Kitterman J.A., Procissi D., Chakkalakal S., Peng C-Y., McGuire T.L., et al. CNS demyelination in fibrodysplasia ossificans progressiva. J Neurol 2012, 259:2644-2655.
27. Ulusoy H. Fibrodysplasia ossificans progressiva without characteristic skeletal anomalies. Rheumatol Int 2012, 32:1379-1382.
28. Whyte M.P., Wenkert D., Demertzis J.L., DiCarlo E.F., Westenberg E., Mumm S. Fibrodysplasia ossificans progressiva: Middle-age onset of heterotopic ossification from a unique missense mutation (c.974G>C, p.G325A) in ACVR1. J Bone Miner Res 2012, 27:729-737.
29. Janoff H.B., Tabas J.A., Shore E.M., Muenke M., Dalinka M.K., Schlesinger S., et al. Mild expression of fibrodysplasia ossificans progressiva: A report of 3 cases. J Rheumatol 1995, 22:976-978.
30. Virdi A.S., Shore E.M., Oreffo R.O., Li M., Connor J.M., Smith R., et al. Phenotypic and molecular heterogeneity in fibrodysplasia ossificans progressiva. Calcif Tissue Int 1999, 65:250-255.
31. Hebela N., Shore E.M., Kaplan F.S. Three pairs of monozygotic twins with fibrodysplasia ossificans progressiva: The role of environment in the progression of heterotopic ossification. Clin Rev Bone Miner Metab 2005, 3:205-208.
32. Kaplan F.S., Xu M., Glaser D.L., Collins F., Connor M., Kitterman J., et al. Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics 2008, 12:1295-1300.
33. Kaplan FS. The medical managment of Fibrodysplasia ossificans progressiva: Current treatment considerations. En: Shore EM, Pignolo RJ, editores. Clin Proc Intl Clin Consort FOP. 2011;4:1-100.
34. Kitterman J.A., Kantanie S., Rocke D.M., Kaplan F.S. Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics 2005, 116:654-661.
35. Zan X., Wang J., You C. The danger of biopsy in fibrodysplasia ossificans progressiva. Arch Dis Child 2012, 97:785-786.
36. Roberts T., Stephen L., Scott C., Urban M., Sudi S., Beighton P. Fibrodysplasia ossificans progressiva (FOP) in South Africa: Dental implications in 5 cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011, 112:11-18.
37. Iber T., Klösel S., Schoenes B., Zacharowski K. Fibrodysplasia ossificans progressiva. Anesthetic management of a 2-year-old child. Anaesthesist 2010, 59:535-538.
38. Gorji R., Li F., Nastasi R., Stuart S. Fibrodysplasia ossificans progressiva: Anesthetic management in complex orthopedic spine procedures. J Clin Anesth 2011, 23:558-561.
39. Shimono K., Tung W-E., Macolino C., Chi A.H-T., Didizian J.H., Mundy C., et al. Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-γ agonists. Nat Med 2011, 17:454-460.
40. Kaplan F.S., Shore E.M. Derailing heterotopic ossification and RARing to go. Nat Med 2011, 17:420-421. Nature Publishing Group.
41. Shore E.M., Xu M., Feldman G.J., Fenstermacher D.A., Cho T-J., Choi I.H., et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet 2006, 38:525-527.
42. Kaplan F.S., Xu M., Seemann P., Connor J.M., Glaser D.L., Carroll L., et al. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat 2009, 30:379-390.
43. Shen Q., Little S.C., Xu M., Haupt J., Ast C., Katagiri T., et al. The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization. J Clin Invest 2009, 119:3462-3472.
44. Fukuda T., Kohda M., Kanomata K., Nojima J., Nakamura A., Kamizono J., et al. Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. J Biol Chem 2009, 284:7149-7156.
45. Urist M.R. Bone: Formation by autoinduction. Science 1965, 150:893-899.
46. Miyazono K., Dijke Ten P., Heldin C.H. TGF-beta signaling by Smad proteins. Adv Immunol 2000, 75:115-157.
47. Massagué J. TGF-beta signal transduction. Annu Rev Biochem 1998, 67:753-791.
48. Shi Y., Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003, 113:685-700.
49. Chen D., Zhao M., Mundy G.R. Bone morphogenetic proteins. Growth Factors 2004, 22:233-241.
50. Yoon B.S., Lyons K.M. Multiple functions of BMPs in chondrogenesis. J Cell Biochem 2004, 93:93-103.
51. Massagué J., Seoane J., Wotton D. Smad transcription factors. Genes Dev 2005, 19:2783-2810.
52. Gazzerro E., Canalis E. Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord 2006, 7:51-65.
53. Wagner T.U. Bone morphogenetic protein signaling in stem cells -one signal, many consequences. FEBS J 2007, 274:2968-2976.
54. Chaikuad A., Alfano I., Kerr G., Sanvitale C.E., Boergermann J.H., Triffitt J.T., et al. Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J Biol Chem 2012, 287:36990-36998.
55. Cabal-Hierro L., Lazo P.S. Signal transduction by tumor necrosis factor receptors. Cell Signal 2012, 24:1297-1305.
56. Marinou K., Christodoulides C., Antoniades C., Koutsilieris M. Wnt signaling in cardiovascular physiology. Trends Endocrinol Metab 2012, 23:582-590.
57. Itoh F., Itoh S., Goumans M-J., Valdimarsdottir G., Iso T., Dotto G.P., et al. Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells. EMBO J 2004, 23:541-551.
58. Kaplan F.S., Groppe J., Pignolo R.J., Shore E.M. Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis. Ann N Y Acad Sci 2007, 1116:113-133.
59. Zhang D., Schwarz E.M., Rosier R.N., Zuscik M.J., Puzas J.E., O'Keefe R.J. ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. J Bone Miner Res 2003, 18:1593-1604.
60. Cai J., Pardali E., Sánchez-Duffhues G., Dijke Ten P. BMP signaling in vascular diseases. FEBS Lett. FEBS 2012, 586:1993-2002.
61. Massagué J., Blain S.W., Lo R.S. TGFbeta signaling in growth control, cancer, and heritable disorders. Cell 2000, 103:295-309.
62. Shafritz A.B., Shore E.M., Gannon F.H., Zasloff M.A., Taub R., Muenke M., et al. Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. N Engl J Med 1996, 335:555-561.
63. Song G-A., Kim H-J., Woo K-M., Baek J-H., Kim G-S., Choi J-Y., et al. Molecular consequences of the ACVR1(R206H) mutation of fibrodysplasia ossificans progressiva. J Biol Chem 2010, 285:22542-22553.
64. van Dinther M., Visser N., de Gorter D.J.J., Doorn J., Goumans M-J., de Boer J., et al. ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation. J Bone Miner Res 2010, 25:1208-1215.
65. Akiyama S., Katagiri T., Namiki M., Yamaji N., Yamamoto N., Miyama K., et al. Constitutively active BMP type I receptors transduce BMP-2 signals without the ligand in C2C12 myoblasts. Exp Cell Res 1997, 235:362-369.
66. Mura M., Cappato S., Giacopelli F., Ravazzolo R., Bocciardi R. The role of the 3'UTR region in the regulation of the ACVR1/Alk-2 gene expression. PLoS ONE 2012, 7:e50958.
67. Kaplan F.S., Tabas J.A., Zasloff M.A. Fibrodysplasia ossificans progressiva: A clue from the fly?. Calcif Tissue Int 1990, 47:117-125.
68. Gannon F.H., Kaplan F.S., Olmsted E., Finkel G.C., Zasloff M.A., Shore E. Bone morphogenetic protein 2/4 in early fibromatous lesions of fibrodysplasia ossificans progressiva. Hum Pathol 1997, 28:339-343.
69. Olmsted E.A., Kaplan F.S., Shore E.M. Bone morphogenetic protein-4 regulation in fibrodysplasia ossificans progressiva. Clin Orthop Relat Res 2003, 408:331-343.
70. La Peña de L.S., Billings P.C., Fiori J.L., Ahn J., Kaplan F.S., Shore E.M. Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA. J Bone Miner Res 2005, 20:1168-1176.
71. Billings P.C., Fiori J.L., Bentwood J.L., O'Connell M.P., Jiao X., Nussbaum B., et al. Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (FOP). J Bone Miner Res 2008, 23:305-313.
72. Le V.Q., Wharton K.A. Hyperactive BMP signaling induced by ALK2(R206H) requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva. Dev Dyn 2012, 241:200-214.
73. Bagarova J., Vonner A.J., Armstrong K.A., Börgermann J., Lai C.S.C., Deng D.Y., et al. Constitutively active ALK2 receptor mutants require type II receptor cooperation. Mol Cell Biol 2013, 33:2413-2424.
74. Chakkalakal S.A., Zhang D., Culbert A.L., Convente M.R., Caron R.J., Wright A.C., et al. An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva. J Bone Miner Res 2012, 27:1746-1756.
75. Matsumoto Y., Hayashi Y., Schlieve C.R., Ikeya M., Kim H., Nguyen T.D., et al. Induced pluripotent stem cells from patients with human fibrodysplasia ossificans progressiva show increased mineralization and cartilage formation. Orphanet J Rare Dis 2013, 8:190.
76. Hamasaki M., Hashizume Y., Yamada Y., Katayama T., Hohjoh H., Fusaki N., et al. Pathogenic mutation of ALK2 inhibits induced pluripotent stem cell reprogramming and maintenance: Mechanisms of reprogramming and strategy for drug identification. Stem Cells 2012, 30:2437-2449.
77. Potenta S., Zeisberg E., Kalluri R. The role of endothelial-to-mesenchymal transition in cancer progression. Br J Cancer 2008, 99:1375-1379.
78. Zeisberg E.M., Potenta S., Xie L., Zeisberg M., Kalluri R. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res 2007, 67:10123-10128.
79. Maddaluno L., Rudini N., Cuttano R., Bravi L., Giampietro C., Corada M., et al. EndMT contributes to the onset and progression of cerebral cavernous malformations. Nature 2013, 498:492-496.
80. Zeisberg E.M., Tarnavski O., Zeisberg M., Dorfman A.L., McMullen J.R., Gustafsson E., et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med 2007, 13:952-961.
81. Zeisberg E.M., Potenta S.E., Sugimoto H., Zeisberg M., Kalluri R. Fibroblasts in kidney fibrosis emerge via endothelial-to-mesenchymal transition. J Am Soc Nephrol 2008, 19:2282-2287.
82. Kizu A., Medici D., Kalluri R. Endothelial-mesenchymal transition as a novel mechanism for generating myofibroblasts during diabetic nephropathy. Am J Pathol 2009, 175:1371-1373.
83. Li J., Qu X., Bertram J.F. Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice. Am J Pathol 2009, 175:1380-1388.
84. Mironov A. Endothelial-mesenchymal transformation in atherosclerosis: A recapitulation of embryonic heart tissue morphogenesis. Ann Biomed Eng 1995, 23(Suppl 1):S29A.
85. Chen P-Y., Qin L., Barnes C., Charisse K., Yi T., Zhang X., et al. FGF regulates TGF-β signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression. Cell Rep 2012, 2:1684-1696.
86. Qiao L., Nishimura T., Shi L., Sessions D., Thrasher A., Trudell J.R., et al. Endothelial fate-mapping in mice with pulmonary hypertension. Circulation 2014, 129:692-703.
87. Arciniegas E., Frid M.G., Douglas I.S., Stenmark K.R. Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2007, 293:L1-L8.
88. Lee J.G., Kay E.P. FGF-2-mediated signal transduction during endothelial mesenchymal transformation in corneal endothelial cells. Exp Eye Res 2006, 83:1309-1316.
89. Lewinson D., Maor G., Rozen N., Rabinovich I., Stahl S., Rachmiel A. Expression of vascular antigens by bone cells during bone regeneration in a membranous bone distraction system. Histochem Cell Biol 2001, 116:381-388.
90. Lounev V.Y., Ramachandran R., Wosczyna M.N., Yamamoto M., Maidment A.D.A., Shore E.M., et al. Identification of progenitor cells that contribute to heterotopic skeletogenesis. J Bone Joint Surg Am 2009, 91:652-663.
91. Hegyi L., Gannon F.H., Glaser D.L., Shore E.M., Kaplan F.S., Shanahan C.M. Stromal cells of fibrodysplasia ossificans progressiva lesions express smooth muscle lineage markers and the osteogenic transcription factor Runx2/Cbfa-1: Clues to a vascular origin of heterotopic ossification?. J Pathol 2003, 201:141-148.
92. Medici D., Shore E.M., Lounev V.Y., Kaplan F.S., Kalluri R., Olsen B.R. Conversion of vascular endothelial cells into multipotent stem-like cells. Nat Med 2010, 16:1400-1406.
93. Yu P.B., Hong C.C., Sachidanandan C., Babitt J.L., Deng D.Y., Hoyng S.A., et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 2008, 4:33-41.
94. Yu P.B., Deng D.Y., Lai C.S., Hong C.C., Cuny G.D., Bouxsein M.L., et al. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med 2008, 14:1363-1369.
95. Mohedas A.H., Xing X., Armstrong K.A., Bullock A.N., Cuny G.D., Yu P.B. Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS Chem Biol 2013, 8:1291-1302.
96. Sanvitale CE, Kerr G, Chaikuad A, Ramel M-C, Mohedas AH, Reichert S, et al. A new class of small molecule inhibitor of BMP signaling. Ghosh D, editor. PLoS ONE. 2013;8:e62721.
97. Shi S., Cai J., de Gorter D.J.J., Sánchez-Duffhues G., Kemaladewi D.U., Hoogaars W.M.H., et al. Antisense-oligonucleotide mediated exon skipping in activin-receptor-like kinase 2: Inhibiting the receptor that is overactive in fibrodysplasia ossificans progressiva. PLoS ONE 2013, 8:e69096.
98. Takahashi M., Katagiri T., Furuya H., Hohjoh H. Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva. Gene Ther 2012, 19:781-785.
99. Amarilio R., Viukov S.V., Sharir A., Eshkar-Oren I., Johnson R.S., Zelzer E. HIF1alpha regulation of Sox9 is necessary to maintain differentiation of hypoxic prechondrogenic cells during early skeletogenesis. Development 2007, 134:3917-3928.
100. Karhausen J., Haase V.H., Colgan S.P. Inflammatory hypoxia: Role of hypoxia-inducible factor. Cell Cycle 2005, 4:256-258.
101. Shore E.M., Kaplan F.S. Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP). Bone 2008, 43:427-433.
102. Kaplan F.S., Glaser D.L., Shore E.M., Pignolo R.J., Xu M., Zhang Y., et al. Hematopoietic stem-cell contribution to ectopic skeletogenesis. JBJS 2007, 89:347-357.
103. Kan L., Liu Y., McGuire T.L., Berger D.M.P., Awatramani R.B., Dymecki S.M., et al. Dysregulation of local stem/progenitor cells as a common cellular mechanism for heterotopic ossification. Stem Cells 2009, 27:150-156.
104. Uccelli A., Moretta L., Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008, 8:726-736.