Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification

Science Translational Medicine

Volumn 8, Issue 366, 2016, Pages

  Dey, Devaveena ^a   Bagarova, Jana ^a   Hatsell, Sarah J ^b   Armstrong, Kelli A ^a   Huang, Lily ^b   Ermann, Joerg ^a   Vonner, Ashley J ^a   Shen, Yue ^a   Mohedas, Agustin H ^a   Lee, Arthur ^c   Eekhoff, Elisabeth M W ^d   Van Schie, Annelies ^d   Demay, Marie B ^e   Keller, Charles ^f   Wagers, Amy J ^g,h   Economides, Aris N ^b,i   Yu, Paul B ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b REGENERON PHARMACEUTICALS INC   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

^d VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

^f Children's Cancer Therapy Development Institute   (United States)

^g HARVARD UNIVERSITY   (United States)

^h JOSLIN DIABETES CENTER   (United States)

ⁱ AB)   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVIN A; BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN RECEPTOR 1; PROTEIN ACVR1; UNCLASSIFIED DRUG; VASCULAR ENDOTHELIAL CADHERIN; ACTIVIN RECEPTOR 1; ACVR1 PROTEIN, MOUSE; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; LIGAND; MX1 PROTEIN, HUMAN; MX1 PROTEIN, MOUSE; MYXOVIRUS RESISTANCE PROTEIN; SCX PROTEIN, MOUSE; SCXA PROTEIN, HUMAN;

ADULT; ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARTILAGE CELL; CONTROLLED STUDY; FEMALE; FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; FLOW CYTOMETRY; GENOTYPE; HETEROTOPIC OSSIFICATION; HETEROZYGOTE; HUMAN; IN VIVO STUDY; LIGAMENT; MALE; MOUSE; NONHUMAN; PERICYTE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; SATELLITE CELL; SIGNAL TRANSDUCTION; TENDON; TRANSGENIC MOUSE; VASCULAR ENDOTHELIUM; VASCULAR SMOOTH MUSCLE; ANIMAL; CELL LINEAGE; CYTOLOGY; DISEASE MODEL; GENE TARGETING; GENETICS; JOINT; METABOLISM; MUTATION; STEM CELL;

ACTIVIN RECEPTORS, TYPE I; ALLELES; ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; BONE MORPHOGENETIC PROTEINS; CELL LINEAGE; DISEASE MODELS, ANIMAL; FEMALE; GENE KNOCK-IN TECHNIQUES; GENOTYPE; HUMANS; JOINTS; LIGAMENTS; LIGANDS; MALE; MICE; MICE, TRANSGENIC; MUTATION; MYXOVIRUS RESISTANCE PROTEINS; OSSIFICATION, HETEROTOPIC; PHENOTYPE; STEM CELLS;

EID: 84997611248     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.aaf1090     Document Type: Article

References (59)

1. F. S. Kaplan, M. Le Merrer, D. L. Glaser, R. J. Pignolo, R. E. Goldsby, J. A. Kitterman, J. Groppe, E. M. Shore, Fibrodysplasia ossificans progressiva. Best Pract. Res. Clin. Rheumatol. 22, 191-205 (2008).
2. R. J. Pignolo, C. Bedford-Gay, M. Liljesthröm, B. P. Durbin-Johnson, E. M. Shore, D. M. Rocke, F. S. Kaplan, The natural history of flare-ups in fibrodysplasia ossificans progressiva (FOP): A comprehensive global assessment. J. Bone Miner. Res. 31, 650-656 (2016).
3. E. M. Shore, M. Xu, G. J. Feldman, D. A. Fenstermacher, T.-J. Cho, I. H. Choi, J. M. Connor, P. Delai, D. L. Glaser, M. LeMerrer, R. Morhat, J. G. Rogers, R. Smith, J. T. Triffitt, J. A. Urtizberea, M. Zasloff, M. A. Brown, F. S. Kaplan, A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat. Genet. 38, 525-527 (2006).
4. F. S. Kaplan, M. Xu, P. Seemann, J. M. Connor, D. L. Glaser, L. Carroll, P. Delai, E. Fastnacht-Urban, S. J. Forman, G. Gillessen-Kaesbach, J. Hoover-Fong, B. Köster, R. M. Pauli, W. Reardon, S.-A. Zaidi, M. Zasloff, R. Morhart, S. Mundlos, J. Groppe, E. M. Shore, Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum. Mutat. 30, 379-390 (2009).
5. T. Fukuda, M. Kohda, K. Kanomata, J. Nojima, A. Nakamura, J. Kamizono, Y. Noguchi, K. Iwakiri, T. Kondo, J. Kurose, K.-i. Endo, T. Awakura, J. Fukushi, Y. Nakashima, T. Chiyonobu, A. Kawara, Y. Nishida, I. Wada, M. Akita, T. Komori, K. Nakayama, A. Nanba, Y. Maruki, T. Yoda, H. Tomoda, P. B. Yu, E. M. Shore, F. S. Kaplan, K. Miyazono, M. Matsuoka, K. Ikebuchi, A. Ohtake, H. Oda, E. Jimi, I. Owan, Y. Okazaki, T. Katagiri, Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. J. Biol. Chem. 284, 7149-7156 (2009).
6. W. Zhang, K. Zhang, L. Song, J. Pang, H. Ma, E. M. Shore, F. S. Kaplan, P. Wang, The phenotype and genotype of fibrodysplasia ossificans progressiva in China: A report of 72 cases. Bone 57, 386-391 (2013).
7. S. J. Hatsell, V. Idone, D. M. A. Wolken, L. Huang, H. J. Kim, L. Wang, X. Wen, K. C. Nannuru, J. Jimenez, L. Xie, N. Das, G. Makhoul, R. Chernomorsky, D. D'Ambrosio, R. A. Corpina, C. J. Schoenherr, K. Feeley, P. B. Yu, G. D. Yancopoulos, A. J. Murphy, A. N. Economides, ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci. Transl. Med. 7, 303-137 (2015).
8. K. Hino, M. Ikeya, K. Horigome, Y. Matsumoto, H. Ebise, M. Nishio, K. Sekiguchi, M. Shibata, S. Nagata, S. Matsuda, J. Toguchida, Neofunction of ACVR1 in fibrodysplasia ossificans progressiva. Proc. Natl. Acad. Sci. U.S.A. 112, 15438-15443 (2015).
9. A. Toom, A. Arend, D. Gunnarsson, R. Ulfsparre, S. Suutre, T. Haviko, G. Selstam, Bone formation zones in heterotopic ossifications: Histologic findings and increased expression of bone morphogenetic protein 2 and transforming growth factors b2 and b3. Calcif. Tissue Int. 80, 259-267 (2007).
10. R. J. Lories, I. Derese, F. P. Luyten, Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J. Clin. Invest. 115, 1571-1579 (2005).
11. F. E. Weber, H. Schmökel, M. Oelgeschläger, J. Nickel, F. E. Maly, P. Hortschansky, K. W. Grätz, Deletion mutants of BMP folding variants act as BMP antagonists and are efficient inhibitors for heterotopic ossification. J. Bone Miner. Res. 18, 2142-2151 (2003).
12. D. Hannallah, H. Peng, B. Young, A. Usas, B. Gearhart, J. Huard, Retroviral delivery of Noggin inhibits the formation of heterotopic ossification induced by BMP-4, demineralized bone matrix, and trauma in an animal model. J. Bone Joint Surg. Am. 86, 80-91 (2004).
13. J. R. Peterson, S. De La Rosa, O. Eboda, K. E. Cilwa, S. Agarwal, S. R. Buchman, P. S. Cederna, C. Xi, M. D. Morris, D. N. Herndon, W. Xiao, R. G. Tompkins, P. H. Krebsbach, S. C. Wang, B. Levi, Treatment of heterotopic ossification through remote ATP hydrolysis. Sci. Transl. Med. 6, 255-132 (2014).
14. A. H. Mohedas, X. Xing, K. A. Armstrong, A. N. Bullock, G. D. Cuny, P. B. Yu, Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS Chem. Biol. 8, 1291-1302 (2013).
15. P. B. Yu, D. Y. Deng, C. S. Lai, C. C. Hong, G. D. Cuny, M. L. Bouxsein, D. W. Hong, P. M. McManus, T. Katagiri, C. Sachidanandan, N. Kamiya, T. Fukuda, Y. Mishina, R. T. Peterson, K. D. Bloch, BMP type I receptor inhibition reduces heterotopic ossification. Nat. Med. 14, 1363-1369 (2008).
16. R. K. Suda, P. C. Billings, K. P. Egan, J.-H. Kim, R. McCarrick-Walmsley, D. L. Glaser, D. L. Porter, E. M. Shore, R. J. Pignolo, Circulating osteogenic precursor cells in heterotopic bone formation. Stem Cells 27, 2209-2219 (2009).
17. L. Kan, C.-Y. Peng, T. L. McGuire, J. A. Kessler, Glast-expressing progenitor cells contribute to heterotopic ossification. Bone 53, 194-203 (2013).
18. T. Oishi, A. Uezumi, A. Kanaji, N. Yamamoto, A. Yamaguchi, H. Yamada, K. Tsuchida, Osteogenic differentiation capacity of human skeletal muscle-derived progenitor cells. PLOS ONE 8, e56641 (2013).
19. S. A. Chakkalakal, D. Zhang, A. L. Culbert, M. R. Convente, R. J. Caron, A. C. Wright, A. D. Maidment, F. S. Kaplan, E. M. Shore, An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva. J. Bone Miner. Res. 27, 1746-1756 (2012).
20. V. Y. Lounev, R. Ramachandran, M. N. Wosczyna, M. Yamamoto, A. D. A. Maidment, E. M. Shore, D. L. Glaser, D. J. Goldhamer, F. S. Kaplan, Identification of progenitor cells that contribute to heterotopic skeletogenesis. J. Bone Joint Surg. Am. 91, 652-663 (2009).
21. M. N. Wosczyna, A. A. Biswas, C. A. Cogswell, D. J. Goldhamer, Multipotent progenitors resident in the skeletal muscle interstitium exhibit robust BMP-dependent osteogenic activity and mediate heterotopic ossification. J. Bone Miner. Res. 27, 1004-1017 (2012).
22. D. Medici, E. M. Shore, V. Y. Lounev, F. S. Kaplan, R. Kalluri, B. R. Olsen, Conversion of vascular endothelial cells into multipotent stem-like cells. Nat. Med. 16, 1400-1406 (2010).
23. R. B. Cohen, G. V. Hahn, J. A. Tabas, J. Peeper, C. L. Levitz, A. Sando, N. Sando, M. Zasloff, F. S. Kaplan, The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J. Bone Joint Surg. Am. 75, 215-219 (1993).
24. I. Hüning, G. Gillessen-Kaesbach, Fibrodysplasia ossificans progressiva: Clinical course, genetic mutations and genotype-phenotype correlation. Mol. Syndromol. 5, 201-211 (2014).
25. R. Smith, N. A. Athanasou, S. E. Vipond, Fibrodysplasia (myositis) ossificans progressiva: Clinicopathological features and natural history. QJM 89, 445-446 (1996).
26. B. A. Pryce, A. E. Brent, N. D. Murchison, C. J. Tabin, R. Schweitzer, Generation of transgenic tendon reporters, ScxGFP and ScxAP, using regulatory elements of the scleraxis gene. Dev. Dyn. 236, 1677-1682 (2007).
27. R. S. Archer, J. I. Bayley, C. W. Archer, S. Y. Ali, Cell and matrix changes associated with pathological calcification of the human rotator cuff tendons. J. Anat. 182 (Pt 1), 1-11 (1993).
28. D. Park, J. A. Spencer, B. I. Koh, T. Kobayashi, J. Fujisaki, T. L. Clemens, C. P. Lin, H. M. Kronenberg, D. T. Scadden, Endogenous bone marrow MSCs are dynamic, fate-restricted participants in bone maintenance and regeneration. Cell Stem Cell 10, 259-272 (2012).
29. M. D. Muzumdar, B. Tasic, K. Miyamichi, L. Li, L. Luo, A global double-fluorescent Cre reporter mouse. Genesis 45, 593-605 (2007).
30. J. de Boer, A. Williams, G. Skavdis, N. Harker, M. Coles, M. Tolaini, T. Norton, K. Williams, K. Roderick, A. J. Potocnik, D. Kioussis, Transgenic mice with hematopoietic and lymphoid specific expression of Cre. Eur. J. Immunol. 33, 314-325 (2003).
31. A. L. Culbert, S. A. Chakkalakal, E. G. Theosmy, T. A. Brennan, F. S. Kaplan, E. M. Shore, Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification. Stem Cells 32, 1289-1300 (2014).
32. D. Zhang, E. M. Schwarz, R. N. Rosier, M. J. Zuscik, J. E. Puzas, R. J. O'Keefe, ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. J. Bone Miner. Res. 18, 1593-1604 (2003).
33. Q. Shen, S. C. Little, M. Xu, J. Haupt, C. Ast, T. Katagiri, S. Mundlos, P. Seemann, F. S. Kaplan, M. C. Mullins, E. M. Shore, The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization. J. Clin. Invest. 119, 3462-3472 (2009).
34. F. S. Kaplan, D. L. Glaser, E. M. Shore, R. J. Pignolo, M. Xu, Y. Zhang, D. Senitzer, S. J. Forman, S. G. Emerson, Hematopoietic stem-cell contribution to ectopic skeletogenesis. J. Bone Joint Surg. Am. 89, 347-357 (2007).
35. H. Hock, E. Meade, S. Medeiros, J. W. Schindler, P. J. M. Valk, Y. Fujiwara, S. H. Orkin, Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. Genes Dev. 18, 2336-2341 (2004).
36. E. Barruet, B. M. Morales, W. Lwin, M. P. White, C. V. Theodoris, H. Kim, A. Urrutia, S. A. Wong, D. Srivastava, E. C. Hsiao, The ACVR1 R206H mutation found in fibrodysplasia ossificans progressiva increases human induced pluripotent stem cell-derived endothelial cell formation and collagen production through BMP-mediated SMAD1/5/8 signaling. Stem Cell Res. Ther. 7, 115 (2016).
37. C. M. Penton, J. M. Thomas-Ahner, E. K. Johnson, C. McAllister, F. Montanaro, Muscle side population cells from dystrophic or injured muscle adopt a fibro-Adipogenic fate. PLOS ONE 8, e54553 (2013).
38. A. Uezumi, T. Ito, D. Morikawa, N. Shimizu, T. Yoneda, M. Segawa, M. Yamaguchi, R. Ogawa, M. M. Matev, Y. Miyagoe-Suzuki, S. Takeda, K. Tsujikawa, K. Tsuchida, H. Yamamoto, S.-i. Fukada, Fibrosis and adipogenesis originate from a common mesenchymal progenitor in skeletal muscle. J. Cell Sci. 124, 3654-3664 (2011).
39. A. Uezumi, S.-i. Fukada, N. Yamamoto, S. Takeda, K. Tsuchida, Mesenchymal progenitors distinct from satellite cells contribute to ectopic fat cell formation in skeletal muscle. Nat. Cell Biol. 12, 143-152 (2010).
40. K. J. Mitchell, A. Pannérec, B. Cadot, A. Parlakian, V. Besson, E. R. Gomes, G. Marazzi, D. A. Sassoon, Identification and characterization of a non-satellite cell muscle resident progenitor during postnatal development. Nat. Cell Biol. 12, 257-266 (2010).
41. N. D. Murchison, B. A. Price, D. A. Conner, D. R. Keene, E. N. Olson, C. J. Tabin, R. Schweitzer, Regulation of tendon differentiation by scleraxis distinguishes force-Transmitting tendons from muscle-Anchoring tendons. Development 134, 2697-2708 (2007).
42. M. J. Mienaltowski, S. M. Adams, D. E. Birk, Regional differences in stem cell/progenitor cell populations from the mouse Achilles tendon. Tissue Eng. Part A 19, 199-210 (2013).
43. J. Bagarova, A. J. Vonner, K. A. Armstrong, J. Börgermann, C. S. C. Lai, D. Y. Deng, H. Beppu, I. Alfano, P. Filippakopoulos, N. W. Morrell, A. N. Bullock, P. Knaus, Y. Mishina, P. B. Yu, Constitutively active ALK2 receptor mutants require type II receptor cooperation. Mol. Cell. Biol. 33, 2413-2424 (2013).
44. A. Chaikuad, I. Alfano, G. Kerr, C. E. Sanvitale, J. H. Boergermann, J. T. Triffitt, F. von Delft, S. Knapp, P. Knaus, A. N. Bullock, Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J. Biol. Chem. 287, 36990-36998 (2012).
45. V. Q. Le, K. A. Wharton, Hyperactive BMP signaling induced by ALK2R206H requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva. Dev. Dyn. 241, 200-214 (2012).
46. B. C. Yaden, Y. X. Wang, J. M. Wilson, A. E. Culver, A. Milner, A. Datta-Mannan, P. Shetler, J. E. Croy, G. Dai, V. Krishnan, Inhibition of activin A ameliorates skeletal muscle injury and rescues contractile properties by inducing efficient remodeling in female mice. Am. J. Pathol. 184, 1152-1166 (2014).
47. J. Zhu, Y. Li, A. Lu, B. Gharaibeh, J. Ma, T. Kobayashi, A. J. Quintero, J. Huard, Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis. Am. J. Pathol. 179, 915-930 (2011).
48. Clementia Pharmaceuticals Inc., An efficacy and safety study of palovarotene to treat preosseous flare-ups in FOP subjects (2014).
49. K. Nishijo, T. Hosoyama, C. R. R. Bjornson, B. S. Schaffer, S. I. Prajapati, A. N. Bahadur, M. S. Hansen, M. C. Blandford, A. T. McCleish, B. P. Rubin, J. A. Epstein, T. A. Rando, M. R. Capecchi, C. Keller, Biomarker system for studying muscle, stem cells, and cancer in vivo. FASEB J. 23, 2681-2690 (2009).
50. C. Keller, B. R. Arenkiel, C. M. Coffin, N. El-Bardeesy, R. A. DePinho, M. R. Capecchi, Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: Cooperativity of Ink4a/ARF and Trp53 loss of function. Genes Dev. 18, 2614-2626 (2004).
51. M. Chen, B. P. Herring, Regulation of microRNAs by Brahma-related gene 1 (Brg1) in smooth muscle cells. J. Biol. Chem. 288, 6397-6408 (2013).
52. J. J. Lepore, L. Cheng, M. Min Lu, P. A. Mericko, E. E. Morrisey, M. S. Parmacek, High-efficiency somatic mutagenesis in smooth muscle cells and cardiac myocytes in SM22a-Cre transgenic mice. Genesis 41, 179-184 (2005).
53. P. A. Koni, S. K. Joshi, U.-A. Temann, D. Olson, L. Burkly, R. A. Flavell, Conditional vascular cell adhesion molecule 1 deletion in mice: Impaired lymphocyte migration to bone marrow. J. Exp. Med. 193, 741-754 (2001).
54. A. Monvoisin, J. A. Alva, J. J. Hofmann, A. C. Zovein, T. F. Lane, M. L. Iruela-Arispe, VE-cadherin-CreERT2 transgenic mouse: A model for inducible recombination in the endothelium. Dev. Dyn. 235, 3413-3422 (2006).
55. X. Zhu, R. A. Hill, D. Dietrich, M. Komitova, R. Suzuki, A. Nishiyama, Age-dependent fate and lineage restriction of single NG2 cells. Development 138, 745-753 (2011).
56. O. Abdel-Wahab, J. Gao, M. Adli, A. Dey, T. Trimarchi, Y. R. Chung, C. Kuscu, T. Hricik, D. Ndiaye-Lobry, L. M. LaFave, R. Koche, A. H. Shih, O. A. Guryanova, E. Kim, S. Li, S. Pandey, J. Y. Shin, L. Telis, J. Liu, P. K. Bhatt, S. Monette, X. Zhao, C. E. Mason, C. Y. Park, B. E. Bernstein, I. Aifantis, R. L. Levine, Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. J. Exp. Med. 210, 2641-2659 (2013).
57. T. Fukuda, G. Scott, Y. Komatsu, R. Araya, M. Kawano, M. K. Ray, M. Yamada, Y. Mishina, Generation of a mouse with conditionally activated signaling through the BMP receptor, ALK2. Genesis 44, 159-167 (2006).
58. A. Ventura, D. G. Kirsch, M. E. McLaughlin, D. A. Tuveson, J. Grimm, L. Lintault, J. Newman, E. E. Reczek, R. Weissleder, T. Jacks, Restoration of p53 function leads to tumour regression in vivo. Nature 445, 661-665 (2007).
59. M. W. Lawlor, M. S. Alexander, M. G. Viola, H. Meng, R. Joubert, V. Gupta, N. Motohashi, R. A. Manfready, C. P. Hsu, P. Huang, A. Buj-Bello, L. M. Kunkel, A. H. Beggs, E. Gussoni, Myotubularin-deficient myoblasts display increased apoptosis, delayed proliferation, and poor cell engraftment. Am. J. Pathol. 181, 961-968 (2012).