Targeting heterotopic ossification by inhibiting activin receptor‑like kinase 2 function (Review)
- Authors:
- Fuli Shi
- Jiayu Gao
- Junrong Zou
- Ying Ying
- Hui Lin
-
Affiliations: Jiangxi Province Key Laboratory of Tumor Pathogens and Molecular Pathology, Department of Pathophysiology, School of Basic Medicine Sciences, Nanchang University Medical College, Nanchang, Jiangxi 330006, P.R. China - Published online on: August 6, 2019 https://doi.org/10.3892/mmr.2019.10556
- Pages: 2979-2989
-
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Edwards DS, Kuhn KM, Potter BK and Forsberg JA: Heterotopic ossification: A review of current understanding, treatment, and future. J Orthop Trauma. 30 (Suppl 3):S27–S30. 2016. View Article : Google Scholar : PubMed/NCBI | |
Hildebrand L, Rossbach B, Kühnen P, Gossen M, Kurtz A, Reinke P, Seemann P and Stachelscheid H: Generation of integration free induced pluripotent stem cells from fibrodysplasia ossificans progressiva (FOP) patients from urine samples. Stem Cell Res. 16:54–58. 2016. View Article : Google Scholar : PubMed/NCBI | |
Shore EM, Ahn J, Jan de Beur S, Li M, Xu M, Gardner RJ, Zasloff MA, Whyte MP, Levine MA and Kaplan FS: Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. N Engl J Med. 346:99–106. 2002. View Article : Google Scholar : PubMed/NCBI | |
Maruyama R and Yokota T: Morpholino-mediated exon skipping targeting human ACVR1/ALK2 for fibrodysplasia ossificans progressiva. Methods Mol Biol. 1828:497–502. 2018. View Article : Google Scholar : PubMed/NCBI | |
Lees-Shepard JB, Yamamoto M, Biswas AA, Stoessel SJ, Nicholas SE, Cogswell CA, Devarakonda PM, Schneider MJ Jr, Cummins SM, Legendre NP, et al: Activin-dependent signaling in fibro/adipogenic progenitors causes fibrodysplasia ossificans progressiva. Nat Commun. 9:4712018. View Article : Google Scholar : PubMed/NCBI | |
Wu M, Chen G and Li YP: TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease. Bone Res. 4:160092016. View Article : Google Scholar : PubMed/NCBI | |
Abula K, Muneta T, Miyatake K, Yamada J, Matsukura Y, Inoue M, Sekiya I, Graf D, Economides AN, Rosen V and Tsuji K: Elimination of BMP7 from the developing limb mesenchyme leads to articular cartilage degeneration and synovial inflammation with increased age. FEBS Lett. 589:1240–1248. 2015. View Article : Google Scholar : PubMed/NCBI | |
Pereda A, Martos-Tello JM, Garin I, Errea-Dorronsoro J and Perez de Nanclares G: Progressive osseous heteroplasia caused by a mosaic GNAS mutation. Clin Endocrinol (Oxf). 88:993–955. 2018. View Article : Google Scholar : PubMed/NCBI | |
Culbert AL, Chakkalakal SA, Theosmy EG, Brennan TA, Kaplan FS and Shore EM: Alk2 regulates early chondrogenic fate in fibrodysplasia ossificans progressiva heterotopic endochondral ossification. Stem Cells. 32:1289–300. 2014. View Article : Google Scholar : PubMed/NCBI | |
Feldman G, Li M, Martin S, Urbanek M, Urtizberea JA, Fardeau M, LeMerrer M, Connor JM, Triffitt J, Smith R, et al: Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31. Am J Hum Genet. 66:128–135. 2000. View Article : Google Scholar : PubMed/NCBI | |
Regard JB, Malhotra D, Gvozdenovic-Jeremic J, Josey M, Chen M, Weinstein LS, Lu J, Shore EM, Kaplan FS and Yang Y: Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification. Nat Med. 19:1505–1512. 2013. View Article : Google Scholar : PubMed/NCBI | |
Forsberg JA, Pepek JM, Wagner S, Wilson K, Flint J, Andersen RC, Tadaki D, Gage FA, Stojadinovic A and Elster EA: Heterotopic ossification in high-energy wartime extremity injuries: Prevalence and risk factors. J Bone Joint Surg Am. 91:1084–1091. 2009. View Article : Google Scholar : PubMed/NCBI | |
Kaplan FS, Le Merrer M, Glaser DL, Pignolo RJ, Goldsby RE, Kitterman JA, Groppe J and Shore EM: Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol. 22:191–205. 2008. View Article : Google Scholar : PubMed/NCBI | |
Kaplan FS, Xu M, Glaser DL, Collins F, Connor M, Kitterman J, Sillence D, Zackai E, Ravitsky V, Zasloff M, et al: Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics. 121:e1295–e1300. 2008. View Article : Google Scholar : PubMed/NCBI | |
Potter BK, Forsberg JA, Davis TA, Evans KN, Hawksworth JS, Tadaki D, Brown TS, Crane NJ, Burns TC, O'Brien FP and Elster EA: Heterotopic ossification following combat-related trauma. J Bone Joint Surg Am. 92 (Suppl 2):S74–S89. 2010. View Article : Google Scholar | |
Kan L and Kessler JA: Animal models of typical heterotopic ossification. J Biomed Biotechnol. 2011:3092872011. View Article : Google Scholar : PubMed/NCBI | |
Alfieri KA, Forsberg JA and Potter BK: Blast injuries and heterotopic ossification. Bone Joint Res. 1:192–197. 2012. View Article : Google Scholar : PubMed/NCBI | |
Shehab D, Elgazzar AH and Collier BD: Heterotopic ossification. J Nucl Med. 43:346–353. 2002.PubMed/NCBI | |
Pavey GJ, Polfer EM, Nappo KE, Tintle SM, Forsberg JA and Potter BK: What risk factors predict recurrence of heterotopic ossification after excision in combat-related amputations? Clin Orthop Relat Res. 473:2814–2824. 2015. View Article : Google Scholar : PubMed/NCBI | |
Gugala Z, Olmsted-Davis EA, Xiong Y, Davis EL and Davis AR: Trauma-induced heterotopic ossification regulates the blood-nerve barrier. Front Neurol. 9:4082018. View Article : Google Scholar : PubMed/NCBI | |
Juarez JK, Wenke JC and Rivera JC: Treatments and preventative measures for trauma-induced heterotopic ossification: A review. Clin Transl Sci. 11:365–370. 2018. View Article : Google Scholar : PubMed/NCBI | |
Carroll SF, Buckley CT and Kelly DJ: Cyclic tensile strain can play a role in directing both intramembranous and endochondral ossification of mesenchymal stem cells. Front Bioeng Biotechnol. 5:732017. View Article : Google Scholar : PubMed/NCBI | |
Upadhyay J, Xie L, Huang L, Das N, Stewart RC, Lyon MC, Palmer K, Rajamani S, Graul C, Lobo M, et al: The expansion of heterotopic bone in fibrodysplasia ossificans progressiva is activin A-dependent. J Bone Miner Res. 32:2489–2499. 2017. View Article : Google Scholar : PubMed/NCBI | |
Xu R, Hu J, Zhou X and Yang Y: Heterotopic ossification: Mechanistic insights and clinical challenges. Bone. 109:134–142. 2018. View Article : Google Scholar : PubMed/NCBI | |
Lounev VY, Ramachandran R, Wosczyna MN, Yamamoto M, Maidment AD, Shore EM, Glaser DL, Goldhamer DJ and Kaplan FS: Identification of progenitor cells that contribute to heterotopic skeletogenesis. J Bone Joint Surg Am. 91:652–663. 2009. View Article : Google Scholar : PubMed/NCBI | |
Glaser DL, Economides AN, Wang L, Liu X, Kimble RD, Fandl JP, Wilson JM, Stahl N, Kaplan FS and Shore EM: In vivo somatic cell gene transfer of an engineered Noggin mutein prevents BMP4-induced heterotopic ossification. J Bone Joint Surg Am. 85:2332–2342. 2003. View Article : Google Scholar : PubMed/NCBI | |
Kan L and Kessler JA: Evaluation of the cellular origins of heterotopic ossification. Orthopedics. 37:329–340. 2014. View Article : Google Scholar : PubMed/NCBI | |
Ji Y, Christopherson GT, Kluk MW, Amrani O, Jackson WM and Nesti LJ: Heterotopic ossification following musculoskeletal trauma: Modeling stem and progenitor cells in their microenvironment. Adv Exp Med Biol. 720:39–50. 2011. View Article : Google Scholar : PubMed/NCBI | |
Medici D, Shore EM, Lounev VY, Kaplan FS, Kalluri R and Olsen BR: Conversion of vascular endothelial cells into multipotent stem-like cells. Nat Med. 16:1400–1406. 2010. View Article : Google Scholar : PubMed/NCBI | |
Olmsted-Davis E, Gannon FH, Ozen M, Ittmann MM, Gugala Z, Hipp JA, Moran KM, Fouletier-Dilling CM, Schumara-Martin S, Lindsey RW, et al: Hypoxic adipocytes pattern early heterotopic bone formation. Am J Pathol. 170:620–632. 2007. View Article : Google Scholar : PubMed/NCBI | |
Olmsted-Davis EA, Salisbury EA, Hoang D, Davis EL, Lazard Z, Sonnet C, Davis TA, Forsberg JA and Davis AR: Progenitors in peripheral nerves launch heterotopic ossification. Stem Cells Transl Med. 6:1109–1119. 2017. View Article : Google Scholar : PubMed/NCBI | |
Gurkan UA, Golden R, Kishore V, Riley CP, Adamec J and Akkus O: Immune and inflammatory pathways are involved in inherent bone marrow ossification. Clin Orthop Relat Res. 470:2528–2540. 2012. View Article : Google Scholar : PubMed/NCBI | |
Luu HH, Song WX, Luo X, Manning D, Luo J, Deng ZL, Montag AG, Haydon RC and He TC: Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells. J Orthop Res. 25:665–677. 2007. View Article : Google Scholar : PubMed/NCBI | |
Chen D, Zhao M and Mundy GR: Bone morphogenetic proteins. Growth Factors. 22:233–241. 2004. View Article : Google Scholar : PubMed/NCBI | |
Rahman MS, Akhtar N, Jamil HM, Banik RS and Asaduzzaman SM: TGF-β/BMP signaling and other molecular events: Regulation of osteoblastogenesis and bone formation. Bone Res. 15005015. | |
Sánchez-Duffhues G, Hiepen C, Knaus P and Ten Dijke P: Bone morphogenetic protein signaling in bone homeostasis. Bone. 80:43–59. 2015. View Article : Google Scholar : PubMed/NCBI | |
Shore EM and Kaplan FS: Role of altered signal transduction in heterotopic ossification and fibrodysplasia ossificans progressiva. Curr Osteoporos Rep. 9:83–88. 2011. View Article : Google Scholar : PubMed/NCBI | |
Bouvard B, Masson C, Legrand E and Audran M: Fibrodysplasia ossificans progressiva. A case report and focus on the BMP signaling pathway. Morphologie. 100:250–255. 2016. View Article : Google Scholar : PubMed/NCBI | |
Kan C, Chen L, Hu Y, Ding N, Lu H, Li Y, Kessler JA and Kan L: Conserved signaling pathways underlying heterotopic ossification. Bone. 109:43–48. 2018. View Article : Google Scholar : PubMed/NCBI | |
Chaikuad A, Alfano I, Kerr G, Sanvitale CE, Boergermann JH, Triffitt JT, von Delft F, Knapp S, Knaus P and Bullock AN: Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J Biol Chem. 287:36990–36998. 2012. View Article : Google Scholar : PubMed/NCBI | |
Dudas M, Sridurongrit S, Nagy A, Okazaki K and Kaartinen V: Craniofacial defects in mice lacking BMP type I receptor Alk2 in neural crest cells. Mech Dev. 121:173–182. 2004. View Article : Google Scholar : PubMed/NCBI | |
Lin H, Ying Y, Wang YY, Wang G, Jiang SS, Huang D, Luo L, Chen YG, Gerstenfeld LC and Luo Z: AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation. Biochim Biophys Acta Mol Cell Res. 1864:2369–2377. 2017. View Article : Google Scholar : PubMed/NCBI | |
Engers DW, Frist AY, Lindsley CW, Hong CC and Hopkins CR: Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of dorsomorphin: The discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett. 23:3248–3252. 2013. View Article : Google Scholar : PubMed/NCBI | |
Machiya A, Tsukamoto S, Ohte S, Kuratani M, Fujimoto M, Kumagai K, Osawa K, Suda N, Bullock AN and Katagiri T: Effects of FKBP12 and type II BMP receptors on signal transduction by ALK2 activating mutations associated with genetic disorders. Bone. 111:101–108. 2018. View Article : Google Scholar : PubMed/NCBI | |
van Dinther M, Visser N, de Gorter DJ, Doorn J, Goumans MJ, de Boer J and ten Dijke P: 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. 25:1208–1215. 2010.PubMed/NCBI | |
Chakkalakal SA, Zhang D, Culbert AL, Convente MR, Caron RJ, Wright AC, Maidment AD, Kaplan FS and Shore EM: An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva. J Bone Miner Res. 27:1746–1756. 2012. View Article : Google Scholar : PubMed/NCBI | |
Hatsell SJ, Idone V, Wolken DM, Huang L, Kim HJ, Wang L, Wen X, Nannuru KC, Jimenez J, Xie L, et al: ACVR1R206H receptor mutation causes fibrodysplasia ossificans progressiva by imparting responsiveness to activin A. Sci Transl Med. 7:303ra1372015. View Article : Google Scholar : PubMed/NCBI | |
Katagiri T: A door opens for fibrodysplasia ossificans progressiva. Trends Biochem Sci. 41:119–121. 2016. View Article : Google Scholar : PubMed/NCBI | |
Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, et al: BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 14:1363–1369. 2008. View Article : Google Scholar : PubMed/NCBI | |
Hino K, Ikeya M, Horigome K, Matsumoto Y, Ebise H, Nishio M, Sekiguchi K, Shibata M, Nagata S, Matsuda S and Toguchida J: Neofunction of ACVR1 in fibrodysplasia ossificans progressiva. Proc Natl Acad Sci USA. 112:15438–15443. 2015. View Article : Google Scholar : PubMed/NCBI | |
Olsen OE, Wader KF, Hella H, Mylin AK, Turesson I, Nesthus I, Waage A, Sundan A and Holien T: Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B. Cell Commun Signal. 13:272015. View Article : Google Scholar : PubMed/NCBI | |
Wang H, Lindborg C, Lounev V, Kim JH, McCarrick-Walmsley R, Xu M, Mangiavini L, Groppe JC, Shore EM, Schipani E, et al: Cellular hypoxia promotes heterotopic ossification by amplifying BMP signaling. J Bone Miner Res. 31:1652–1665. 2016. View Article : Google Scholar : PubMed/NCBI | |
Kent WT, Shelton TJ and Eastman J: Heterotopic ossification around the knee after tibial nailing and ipsilateral antegrade and retrograde femoral nailing in the treatment of floating knee injuries. Int Orthop. 42:1379–1385. 2018. View Article : Google Scholar : PubMed/NCBI | |
Wang YK, Sun WF, Liu XG, Deng J, Yan BE, Jiang WY and Lin XB: Comparative study of serum levels of BMP-2 and heterotopic ossification in traumatic brain injury and fractures patients. Zhongguo Gu Shang. 24:399–403. 2011.(In Chinese). PubMed/NCBI | |
Peterson JR, De La Rosa S, Eboda O, Cilwa KE, Agarwal S, Buchman SR, Cederna PS, Xi C, Morris MD, Herndon DN, et al: Treatment of heterotopic ossification through remote ATP hydrolysis. Sci Transl Med. 6:255ra1322014. View Article : Google Scholar : PubMed/NCBI | |
Kang H, Dang AB, Joshi SK, Halloran B, Nissenson R, Zhang X, Li J, Kim HT and Liu X: Novel mouse model of spinal cord injury-induced heterotopic ossification. J Rehabil Res Dev. 51:1109–1118. 2014. View Article : Google Scholar : PubMed/NCBI | |
Lengner CJ, Lepper C, van Wijnen AJ, Stein JL, Stein GS and Lian JB: Primary mouse embryonic fibroblasts: A model of mesenchymal cartilage formation. J Cell Physiol. 200:327–333. 2004. View Article : Google Scholar : PubMed/NCBI | |
Sun E and Hanyu-Deutmeyer AA: Heterotopic Ossification. StatPearlsTreasure Island (FL): StatPearls Publishing StatPearls Publishing LLC; 2018 | |
Beckmann JT, Wylie JD, Potter MQ, Maak TG, Greene TH and Aoki SK: Effect of naproxen prophylaxis on heterotopic ossification following hip arthroscopy: A double-blind randomized placebo-controlled trial. J Bone Joint Surg Am. 97:2032–2037. View Article : Google Scholar : PubMed/NCBI | |
Rivera JC, Hsu JR, Noel SP, Wenke JC and Rathbone CR: Locally delivered nonsteroidal antiinflammatory drug: A potential option for heterotopic ossification prevention. Clin Transl Sci. 8:591–593. 2015. View Article : Google Scholar : PubMed/NCBI | |
Rath E, Warschawski Y, Maman E, Dolkart O, Sharfman ZT, Salai M and Amar E: Selective COX-2 inhibitors significantly reduce the occurrence of heterotopic ossification after Hip arthroscopic surgery. Am J Sports Med. 44:677–681. 2016. View Article : Google Scholar : PubMed/NCBI | |
Beckmann JT, Wylie JD, Kapron AL, Hanson JA, Maak TG and Aoki SK: The effect of NSAID prophylaxis and operative variables on heterotopic ossification after Hip arthroscopy. Am J Sports Med. 42:1359–1364. 2014. View Article : Google Scholar : PubMed/NCBI | |
Haran M, Bhuta T and Lee B: Pharmacological interventions for treating acute heterotopic ossification. Cochrane Database Syst Rev. CD0033212004.PubMed/NCBI | |
Salazar D, Golz A, Israel H and Marra G: Heterotopic ossification of the elbow treated with surgical resection: Risk factors, bony ankylosis, and complications. Clin Orthop Relat Res. 472:2269–2275. 2014. View Article : Google Scholar : PubMed/NCBI | |
Sheybani A, TenNapel MJ, Lack WD, Clerkin P, Hyer DE, Sun W and Jacobson GM: Risk of radiation-induced malignancy with heterotopic ossification prophylaxis: A case-control analysis. Int J Radiat Oncol Biol Phys. 89:584–589. 2014. View Article : Google Scholar : PubMed/NCBI | |
Kaplan FS, Pignolo RJ, Al Mukaddam MM and Shore EM: Hard targets for a second skeleton: Therapeutic horizons for fibrodysplasia ossificans progressiva (FOP). Expert Opin Orphan Drugs. 5:291–294. 2017. View Article : Google Scholar : PubMed/NCBI | |
Cappato S, Tonachini L, Giacopelli F, Tirone M, Galietta LJ, Sormani M, Giovenzana A, Spinelli AE, Canciani B, Brunelli S, et al: High-throughput screening for modulators of ACVR1 transcription: Discovery of potential therapeutics for fibrodysplasia ossificans progressiva. Dis Model Mech. 9:685–696. 2016. View Article : Google Scholar : PubMed/NCBI | |
Glister C, Regan SL, Samir M and Knight P: Gremlin, Noggin, Chordin and follistatin differentially modulate BMP induced suppression of androgen secretion by bovine ovarian theca cells. J Mol Endocrinol. Oct 1–2018.(Epub ahead of print). PubMed/NCBI | |
Yu PB, Hong CC, Sachidanandan C, Babitt JL, Deng DY, Hoyng SA, Lin HY, Bloch KD and Peterson RT: Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol. 4:33–41. 2008. View Article : Google Scholar : PubMed/NCBI | |
Cuny GD, Yu PB, Laha JK, Xing X, Liu JF, Lai CS, Deng DY, Sachidanandan C, Bloch KD and Peterson RT: Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors. Bioorg Med Chem Lett. 18:4388–4392. 2008. View Article : Google Scholar : PubMed/NCBI | |
Mohedas AH, Xing X, Armstrong KA, Bullock AN, Cuny GD and Yu PB: Development of an ALK2-biased BMP type I receptor kinase inhibitor. ACS Chem Biol. 8:1291–1302. 2013. View Article : Google Scholar : PubMed/NCBI | |
Hao J, Ho JN, Lewis JA, Karim KA, Daniels RN, Gentry PR, Hopkins CR, Lindsley CW and Hong CC: In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS Chem Biol. 5:245–253. 2010. View Article : Google Scholar : PubMed/NCBI | |
Tsugawa D, Oya Y, Masuzaki R, Ray K, Engers DW, Dib M, Do N, Kuramitsu K, Ho K, Frist A, et al: Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration. J Pharmacol Exp Ther. 351:549–558. 2014. View Article : Google Scholar : PubMed/NCBI | |
Mohedas AH, Wang Y, Sanvitale CE, Canning P, Choi S, Xing X, Bullock AN, Cuny GD and Yu PB: Structure-activity relationship of 3,5-diaryl-2-aminopyridine ALK2 inhibitors reveals unaltered binding affinity for fibrodysplasia ossificans progressiva causing mutants. J Med Chem. 57:7900–7915. View Article : Google Scholar : PubMed/NCBI | |
Williams E and Bullock AN: Structural basis for the potent and selective binding of LDN-212854 to the BMP receptor kinase ALK2. Bone. 109:251–258. 2018. View Article : Google Scholar : PubMed/NCBI | |
Dey D, Bagarova J, Hatsell SJ, Armstrong KA, Huang L, Ermann J, Vonner AJ, Shen Y, Mohedas AH, Lee A, et al: Two tissue-resident progenitor lineages drive distinct phenotypes of heterotopic ossification. Sci Transl Med. 8:366ra1632016. View Article : Google Scholar : PubMed/NCBI | |
Giacopelli F, Cappato S, Tonachini L, Mura M, Di Lascio S, Fornasari D, Ravazzolo R and Bocciardi R: Identification and characterization of regulatory elements in the promoter of ACVR1, the gene mutated in Fibrodysplasia Ossificans Progressiva. Orphanet J Rare Dis. 8:1452013. View Article : Google Scholar : PubMed/NCBI | |
Li L, Liu Y, Guo Y, Liu B, Zhao Y, Li P, Song F, Zheng H, Yu J, Song T, et al: Regulatory MiR-148a-ACVR1/BMP circuit defines a cancer stem cell-like aggressive subtype of hepatocellular carcinoma. Hepatology. 61:574–584. 2015. View Article : Google Scholar : PubMed/NCBI | |
Zumbrennen-Bullough KB, Wu Q, Core AB, Canali S, Chen W, Theurl I, Meynard D and Babitt JL: MicroRNA-130a is up-regulated in mouse liver by iron deficiency and targets the bone morphogenetic protein (BMP) receptor ALK2 to attenuate BMP signaling and hepcidin transcription. J Biol Chem. 289:23796–23808. 2014. View Article : Google Scholar : PubMed/NCBI | |
Song H, Wang Q, Wen J, Liu S, Gao X, Cheng J and Zhang D: ACVR1, a therapeutic target of fibrodysplasia ossificans progressiva, is negatively regulated by miR-148a. Int J Mol Sci. 13:2063–2077. 2012. View Article : Google Scholar : PubMed/NCBI | |
Mura M, Cappato S, Giacopelli F, Ravazzolo R and Bocciardi R: The role of the 3′UTR region in the regulation of the ACVR1/Alk-2 gene expression. PLoS One. 7:e509582012. View Article : Google Scholar : PubMed/NCBI | |
Karbiener M, Neuhold C, Opriessnig P, Prokesch A, Bogner-Strauss JG and Scheideler M: MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and ALK2. RNA Biol. 8:850–860. 2011. View Article : Google Scholar : PubMed/NCBI | |
Shi S, Cai J, de Gorter DJ, Sanchez-Duffhues G, Kemaladewi DU, Hoogaars WM, Aartsma-Rus A, 't Hoen PA and ten Dijke P: Antisense-oligonucleotide mediated exon skipping in activin-receptor-like kinase 2: Inhibiting the receptor that is overactive in fibrodysplasia ossificans progressiva. PLoS One. 8:e690962013. View Article : Google Scholar : PubMed/NCBI | |
Takahashi M, Katagiri T, Furuya H and Hohjoh H: Disease-causing allele-specific silencing against the ALK2 mutants, R206H and G356D, in fibrodysplasia ossificans progressiva. Gene Ther. 19:781–785. 2012. View Article : Google Scholar : PubMed/NCBI | |
Kaplan J, Kaplan FS and Shore EM: Restoration of normal BMP signaling levels and osteogenic differentiation in FOP mesenchymal progenitor cells by mutant allele-specific targeting. Gene Ther. 19:786–790. 2012. View Article : Google Scholar : PubMed/NCBI | |
Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar I, van Deutekom J, van Ommen GJ and den Dunnen JT: Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat. 30:293–299. 2009. View Article : Google Scholar : PubMed/NCBI | |
Miki Y, Morioka T, Shioi A, Fujimoto K, Sakura T, Uedono H, Kakutani Y, Ochi A, Mori K, Shoji T, et al: Oncostatin M induces C2C12 myotube atrophy by modulating muscle differentiation and degradation. Biochem Biophys Res Commun. 516:951–956. 2019. View Article : Google Scholar : PubMed/NCBI | |
Yamamoto R, Matsushita M, Kitoh H, Masuda A, Ito M, Katagiri T, Kawai T, Ishiguro N and Ohno K: Clinically applicable antianginal agents suppress osteoblastic transformation of myogenic cells and heterotopic ossifications in mice. J Bone Miner Metab. 31:26–33. 2013.PubMed/NCBI | |
Kitoh H, Achiwa M, Kaneko H, Mishima K, Matsushita M, Kadono I, Horowitz JD, Sallustio BC, Ohno K and Ishiguro N: Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: An open-labeled clinical trial. Orphanet J Rare Dis. 8:1632013. View Article : Google Scholar : PubMed/NCBI | |
Kaplan FS, Pignolo RJ and Shore EM: From mysteries to medicines: Drug development for fibrodysplasia ossificans progressive. Expert Opin Orphan Drugs. 1:637–649. 2013. View Article : Google Scholar : PubMed/NCBI | |
Cappato S, Giacopelli F, Ravazzolo R and Bocciardi R: The horizon of a therapy for rare genetic diseases: A ‘Druggable’ future for fibrodysplasia ossificans progressiva. Int J Mol Sci. 19(pii): E9892018. View Article : Google Scholar : PubMed/NCBI | |
Pang J, Zuo Y, Chen Y, Song L, Zhu Q, Yu J, Shan C, Cai Z, Hao J, Kaplan FS, et al: ACVR1-Fc suppresses BMP signaling and chondro-osseous differentiation in an in vitro model of Fibrodysplasia ossificans progressiva. Bone. 92:29–36. 2016. View Article : Google Scholar : PubMed/NCBI |