Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification

Stem Cells

Volumn 32, Issue 5, 2014, Pages 1289-1300

  Culbert, Andria L ^a   Chakkalakal, Salin A ^a   Theosmy, Edwin G ^a   Brennan, Tracy A ^b   Kaplan, Frederick S ^a,b   Shore, Eileen M ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Alk2; Bone morphogenetic protein signaling; Chondrogenesis; Endochondral ossification; Fibrodysplasia ossificans progressiva

Indexed keywords

ALK2 PROTEIN; BONE MORPHOGENETIC PROTEIN RECEPTOR 1; BONE MORPHOGENETIC PROTEIN RECEPTOR 1A; BONE MORPHOGENETIC PROTEIN RECEPTOR 1B; REGULATOR PROTEIN; UNCLASSIFIED DRUG; ACTIVIN RECEPTOR 1; ACVR1 PROTEIN, MOUSE; BMPR1A PROTEIN, MOUSE; BMPR1B PROTEIN, MOUSE; BMPR2 PROTEIN, MOUSE; BONE MORPHOGENETIC PROTEIN 4; BONE MORPHOGENETIC PROTEIN RECEPTOR 2;

ANIMAL CELL; ARTICLE; CELL DIFFERENTIATION; CELL FATE; CHONDROGENESIS; CONTROLLED STUDY; EMBRYO; GAIN OF FUNCTION MUTATION; GENE CONTROL; IN VIVO STUDY; INTRACELLULAR SIGNALING; LOSS OF FUNCTION MUTATION; MESENCHYMAL STEM CELL; MOUSE; NONHUMAN; OSSIFYING MYOSITIS; PROTEIN EXPRESSION; RECEPTOR SENSITIVITY; REGULATORY MECHANISM; WILD TYPE; ANIMAL; ANIMAL EMBRYO; C57BL MOUSE; CARTILAGE CELL; CELL CULTURE; CYTOLOGY; DRUG EFFECTS; FIBROBLAST; GENETICS; HETEROTOPIC OSSIFICATION; IMMUNOBLOTTING; KNOCKOUT MOUSE; MESENCHYMAL STROMA CELL; METABOLISM; PATHOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TIME; TRANSGENIC MOUSE;

ACTIVIN RECEPTORS, TYPE I; ANIMALS; BONE MORPHOGENETIC PROTEIN 4; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE I; BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II; CELL DIFFERENTIATION; CELLS, CULTURED; CHONDROCYTES; CHONDROGENESIS; EMBRYO, MAMMALIAN; FIBROBLASTS; IMMUNOBLOTTING; MESENCHYMAL STROMAL CELLS; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; MYOSITIS OSSIFICANS; OSSIFICATION, HETEROTOPIC; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TIME FACTORS;

EID: 84899008454     PISSN: 10665099     EISSN: 15494918     Source Type: Journal    
DOI: 10.1002/stem.1633     Document Type: Article

References (57)

1. Mackie EJ, Tatarczuch L, Mirams M,. The skeleton: A multi-functional complex organ: The growth plate chondrocyte and endochondral ossification. J Endocrinol 2011; 211: 109-121.
2. Shore EM, Kaplan FS,. Inherited human diseases of heterotopic bone formation. Nat Rev Rheumatol 2010; 6: 518-527.
3. Forsberg JA, Potter BK,. Heterotopic ossification in wartime wounds. J Surg Orthop Adv 2010; 19: 54-61.
4. Cremin B, Connor JM, Beighton P,. The radiological spectrum of fibrodysplasia ossificans progressiva. Clin Radiol 1982; 33: 499-508.
5. Kaplan FS, Xu M, Seemann P, 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.
6. Shore EM, Xu M, Feldman GJ, 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.
7. Lounev VY, Ramachandran R, Wosczyna MN, et al. Identification of progenitor cells that contribute to heterotopic skeletogenesis. J Bone Joint Surg Am 2009; 91: 652-663.
8. Medici D, Shore EM, Lounev VY, et al. Conversion of vascular endothelial cells into multipotent stem-like cells. Nat Med 2010; 16: 1400-1406.
9. Wosczyna MN, Biswas AA, Cogswell CA, et al. Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust Bmp-dependent osteogenic activity and mediate heterotopic ossification. J Bone Miner Res 2012; 27: 1004-1017.
10. Gannon FH, Valentine BA, Shore EM, et al. Acute lymphocytic infiltration in an extremely early lesion of fibrodysplasia ossificans progressiva. Clin Orthop Relat Res 1998: 19-25.
11. Kaplan FS, Tabas JA, Gannon FH, et al. The histopathology of fibrodysplasia ossificans progressiva. An endochondral process. J Bone Joint Surg Am 1993; 75: 220-230.
12. Culbert AL, Chakkalakal SA, Convente MR, et al. Fibrodysplasia (myositis) ossificans progressiva. In:, Thakker RV, Whyte MP, Eisman JA, Igarashi T, eds. Genetics of Bone Biology and Skeletal Disease. New York, NY: Elsevier, 2013: 375-396.
13. Sieber C, Kopf J, Hiepen C, et al. Recent advances in bmp receptor signaling. Cytokine Growth Factor Rev 2009; 20: 343-355.
14. Derynck R, Zhang YE,. Smad-dependent and smad-independent pathways in Tgf-beta family signalling. Nature 2003; 425: 577-584.
15. Groppe JC, Shore EM, Kaplan FS,. Functional modeling of the Acvr1 (R206h) mutation in Fop. Clin Orthop Relat Res 2007; 462: 87-92.
16. Chaikuad A, Alfano I, Kerr G, et al. Structure of the bone morphogenetic protein receptor Alk2 and implications for fibrodysplasia ossificans progressiva. J Biol Chem 2012; 287: 36990-36998.
17. Shen Q, Little SC, Xu M, et al. The fibrodysplasia ossificans progressiva R206h Acvr1 mutation activates Bmp-independent chondrogenesis and zebrafish embryo ventralization. J Clin Invest 2009; 119: 3462-3472.
18. van Dinther M, Visser N, de Gorter DJ, 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.
19. Pizette S, Niswander L,. Bmps are required at two steps of limb chondrogenesis: Formation of prechondrogenic condensations and their differentiation into chondrocytes. Dev Biol 2000; 219: 237-249.
20. Valcourt U, Gouttenoire J, Moustakas A, et al. Functions of transforming growth factor-beta family type i receptors and smad proteins in the hypertrophic maturation and osteoblastic differentiation of chondrocytes. J Biol Chem 2002; 277: 33545-33558.
21. Zou H, Wieser R, Massague J, et al. Distinct roles of type i bone morphogenetic protein receptors in the formation and differentiation of cartilage. Genes Dev 1997; 11: 2191-2203.
22. Retting KN, Song B, Yoon BS, et al. Bmp canonical smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development 2009; 136: 1093-1104.
23. Fiori JL, Billings PC, de la Pena LS, et al. Dysregulation of the Bmp-P38 Mapk signaling pathway in cells from patients with fibrodysplasia ossificans progressiva (Fop). J Bone Miner Res 2006; 21: 902-909.
24. Billings PC, Fiori JL, Bentwood JL, 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.
25. Fukuda T, Kohda M, Kanomata K, 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.
26. Chakkalakal SA, Zhang D, Culbert AL, et al. An Acvr1 R206h knock-in mouse has fibrodysplasia ossificans progressiva. J Bone Miner Res 2012; 27: 1746-1756.
27. Kaartinen V, Nagy A,. Removal of the floxed neo gene from a conditional knockout allele by the adenoviral Cre recombinase in vivo. Genesis 2001; 31: 126-129.
28. Hayashi S, McMahon AP,. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: A tool for temporally regulated gene activation/inactivation in the mouse. Dev Biol 2002; 244: 305-318.
29. Okabe M, Ikawa M, Kominami K, et al. 'Green Mice' as a source of ubiquitous green cells. FEBS Lett 1997; 407: 313-319.
30. Xu J,. Preparation, culture, and immortalization of mouse embryonic fibroblasts. Curr Protoc Mol Biol 2005;Chapter 28: Unit 28 21.
31. De Ceuninck F, Lesur C, Pastoureau P, et al. Culture of chondrocytes in alginate beads. Methods Mol Med 2004; 100: 15-22.
32. Glaser DL, Economides AN, Wang L, et al. In vivo somatic cell gene transfer of an engineered noggin mutein prevents Bmp4-induced heterotopic ossification. J Bone Joint Surg Am 2003; 85-A: 2332-2342.
33. Rosen AB, Kelly DJ, Schuldt AJ, et al. Finding fluorescent needles in the cardiac haystack: Tracking human mesenchymal stem cells labeled with quantum dots for quantitative in vivo three-dimensional fluorescence analysis. Stem Cells 2007; 25: 2128-2138.
34. Nowalk JR, Flick LM,. Visualization of different tissues involved in endochondral ossification with alcian blue hematoxylin and orange G/eosin counterstain. J Histotechnol 2008; 31: 19-21.
35. Hollnagel A, Oehlmann V, Heymer J, et al. Id genes are direct targets of bone morphogenetic protein induction in embryonic stem cells. J Biol Chem 1999; 274: 19838-19845.
36. de la Pena LS, Billings PC, Fiori JL, et al. 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.
37. Rodrigues M, Griffith LG, Wells A,. Growth factor regulation of proliferation and survival of multipotential stromal cells. Stem Cell Res Ther 2010; 1: 32.
38. Vortkamp A,. Interaction of growth factors regulating chondrocyte differentiation in the developing embryo. Osteoarthritis Cartilage 2001; 9 Suppl A: S109-117.
39. Xu RH, Peck RM, Li DS, et al. Basic Fgf and suppression of Bmp signaling sustain undifferentiated proliferation of human ES Cells. Nat Methods 2005; 2: 185-190.
40. Gannon FH, Kaplan FS, Olmsted E, et al. Bone morphogenetic protein 2/4 in early fibromatous lesions of fibrodysplasia ossificans progressiva. Hum Pathol 1997; 28: 339-343.
41. Garreta E, Genove E, Borros S, et al. Osteogenic differentiation of mouse embryonic stem cells and mouse embryonic fibroblasts in a three-dimensional self-assembling peptide scaffold. Tissue Eng 2006; 12: 2215-2227.
42. Kim KA, Kim JH, Wang Y, et al. Pref-1 (preadipocyte factor 1) activates the Mek/extracellular signal-regulated kinase pathway to inhibit adipocyte differentiation. Mol Cell Biol 2007; 27: 2294-2308.
43. Lengner CJ, Lepper C, van Wijnen AJ, et al. Primary mouse embryonic fibroblasts: A model of mesenchymal cartilage formation. J Cell Physiol 2004; 200: 327-333.
44. Saeed H, Taipaleenmaki H, Aldahmash AM, et al. Mouse embryonic fibroblasts (Mef) exhibit a similar but not identical phenotype to bone marrow stromal stem cells (BMSC). Stem Cell Rev 2012; 8: 318-328.
45. Lefebvre V, Behringer RR, de Crombrugghe B,. L-Sox5, Sox6 and Sox9 control essential steps of the chondrocyte differentiation pathway. Osteoarthritis Cartilage 2001; 9 Suppl A: S69-75.
46. Murtaugh LC, Zeng L, Chyung JH, et al. The chick transcriptional repressor Nkx3.2 acts downstream of Shh to promote bmp-dependent axial chondrogenesis. Dev Cell 2001; 1: 411-422.
47. Bi W, Deng JM, Zhang Z, et al. Sox9 is required for cartilage formation. Nat Genet 1999; 22: 85-89.
48. Lefebvre V, Smits P,. Transcriptional control of chondrocyte fate and differentiation. Birth Defects Res C Embryo Today 2005; 75: 200-212.
49. Qi C, Surapureddi S, Zhu YJ, et al. Transcriptional coactivator Prip, the peroxisome proliferator-activated receptor gamma (Ppargamma)-interacting protein, is required for Ppargamma-mediated adipogenesis. J Biol Chem 2003; 278: 25281-25284.
50. Quintana L, Muinos TF, Genove E, et al. Early tissue patterning recreated by mouse embryonic fibroblasts in a three-dimensional environment. Tissue Eng Part A 2009; 15: 45-54.
51. Huang E, Bi Y, Jiang W, et al. Conditionally immortalized mouse embryonic fibroblasts retain proliferative activity without compromising multipotent differentiation potential. PLoS One 2012; 7: e32428.
52. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 2006; 8: 315-317.
53. Yoon BS, Lyons KM,. Multiple functions of BMPs in chondrogenesis. J Cell Biochem 2004; 93: 93-103.
54. Zhang D, Schwarz EM, Rosier RN, et al. 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.
55. Yoon BS, Ovchinnikov DA, Yoshii I, et al. Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo. Proc Natl Acad Sci USA 2005; 102: 5062-5067.
56. Little SC, Mullins MC,. Bone morphogenetic protein heterodimers assemble heteromeric type i receptor complexes to pattern the dorsoventral axis. Nat Cell Biol 2009; 11: 637-643.
57. Dudas M, Sridurongrit S, Nagy A, et al. Craniofacial defects in mice lacking BMP type I receptor Alk2 in neural crest cells. Mech Dev 2004; 121: 173-182.