Defective proteolytic processing of fibrillar procollagens and prodecorin due to biallelic BMP1 mutations results in a severe, progressive form of osteogenesis imperfecta
BMP1; BONE MORPHOGENETIC PROTEIN-1; MAMMALIAN TOLLOID; STEOGENESIS IMPERFECTA; PRODECORIN
Abstract :
[en] Whereas the vast majority of osteogenesis imperfecta (OI) is caused by autosomal dominant defects in the genes encoding type I procollagen, mutations in a myriad of genes affecting type I procollagen biosynthesis or bone formation and homeostasis have now been associated with rare autosomal recessive OI forms. Recently, homozygous or compound heterozygous mutations in BMP1, encoding the metalloproteases bone morphogenetic protein-1 (BMP1) and its longer isoform mammalian Tolloid (mTLD), were identified in 5 children with a severe autosomal recessive form of OI and in 4 individuals with mild to moderate bone fragility. BMP1/
mTLD functions as the procollagen carboxy-(C)-proteinase for types I to III procollagen but was also suggested to participate in amino-(N)-propeptide cleavage of types V and XI procollagens and in proteolytic trimming of other extracellular matrix (ECM) substrates. We report the phenotypic characteristics and natural history of 4 adults with severe, progressive OI characterized by numerous fractures, short stature with rhizomelic shortening, and deformity of the limbs and variable kyphoscoliosis, in whom we identified novel biallelic missense and frameshift mutations in BMP1. We show that BMP1/mTLD-deficiency in humans not only
results in delayed cleavage of the type I procollagen C-propeptide but also hampers the processing of the small leucine-rich proteoglycan prodecorin, a regulator of collagen fibrillogenesis. Immunofluorescent staining of types I and V collagen and transmission electron microscopy of the dermis show impaired assembly of heterotypic type I/V collagen fibrils in the ECM. Our study thus highlights the severe and progressive nature of BMP1-associated OI in adults and broadens insights into the functional consequences of BMP1/mTLD-deficiency on ECM organization.
Research Center/Unit :
FWO - Fonds Wetenschappelijk Onderzoek Vlaanderen
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Six, Delfien; Ghent University Hospital, Ghent, Belgium > Center of Medical Genetics
Brecht, Guillemyn; Ghent University Hospital, Ghent, Belgium > Center of Medical Genetics
Symoens, Sofie; Ghent University Hospital, Ghent, Belgium > Center of Medical Genetics
Sousa, Ana Berta; Hospital de Santa Maria de Lisboa, Lisbon, Portugal > Department of Genetics,
Medeira, Ana; Hospital de Santa Maria de Lisboa, Lisbon, Portugal > Department of Genetics
Whiteford, Margo; Southern General Hospital, Glasgow, United Kingdom > Department of Clinical Genetics
Hermanns-Lê, Trinh ; Université de Liège > Département des sciences cliniques > Dermatopathologie
Coucke, Paul J; Ghent University Hospital, Ghent, Belgium > Center of Medical Genetics
De Paepe, Anne; Ghent University Hospital, Ghent, Belgium > Center of Medical Genetics
Malfait, Fransiska; Ghent University Hospital, Ghent, Belgium > Center of Medical Genetics
Language :
English
Title :
Defective proteolytic processing of fibrillar procollagens and prodecorin due to biallelic BMP1 mutations results in a severe, progressive form of osteogenesis imperfecta
Publication date :
2015
Journal title :
Journal of Bone and Mineral Research
ISSN :
0884-0431
eISSN :
1523-4681
Publisher :
Wiley-Blackwell, Washington, United States - District of Columbia
Marini, J.C., Forlino, A., Cabral, W.A., Consortium for osteogenesis imperfecta mutations in the helical domain of type i collagen: Regions rich in lethal mutations align with collagen binding sites for integrins and proteoglycans (2007) Hum Mutat., 28 (3), pp. 209-221
Rohrbach, M., Giunta, C., Recessive osteogenesis imperfecta: Clinical, radiological, and molecular findings (2012) Am J Med Genet C Semin Med Genet, 160 C (3), pp. 175-189. , Unger S. Bonafé L. Superti-Furga A. editors
Marini, J.C., Reich, A., Smith, S.M., Osteogenesis imperfecta due to mutations in non-collagenous genes: Lessons in the biology of bone formation (2014) Curr Opin Pediatr., 26 (4), pp. 500-507
Martínez-Glez, V., Valencia, M., Caparrõs-Martin, J.A., Identification of a mutation causing deficient BMP1/mTLD proteolytic activity in autosomal recessive osteogenesis imperfecta (2012) Hum Mutat., 33 (2), pp. 343-350
Asharani, P.V., Keupp, K., Semler, O., Attenuated BMP1 function compromises osteogenesis, leading to bone fragility in humans and zebrafish (2012) Am J Hum Genet., 90 (4), pp. 661-674
Valencia, M., Caparrõs-Martin, J.A., Sirerol-Piquer, M.S., Report of a newly indentified patient with mutations in BMP1 and underlying pathogenetic aspects (2014) Am J Med Genet A., 164 (5), pp. 1143-1150
Fahiminiya, S., Al-Jallad, H., Majewski, J., A polyadenylation site variant causes transcript-specific BMP1 deficiency and frequent fractures in children (2015) Hum Mol Genet., 24 (2), pp. 516-524
Takahara, K., Lyons, G.E., Greenspan, D.S., Bone morphogenetic protein-1 and a mammalian tolloid homologue (mTld) are encoded by alternatively spliced transcripts which are differentially expressed in some tissues (1994) J Biol Chem., 269 (51), pp. 32572-32578
Scott, I.C., Blitz, I.L., Pappano, W.N., Mammalian BMP-1/Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeletogenesis (1999) Dev Biol., 213 (2), pp. 283-300
Suzuki, N., Labosky, P.A., Furuta, Y., Failure of ventral body wall closure in mouse embryos lacking a procollagen C-proteinase encoded by Bmp1, a mammalian gene related to Drosophila tolloid (1996) Development., 122 (11), pp. 3587-3595
Pappano, W.N., Steiglitz, B.M., Scott, I.C., Keene, D.R., Greenspan, D.S., Use of Bmp1/Tll1 doubly homozygous null mice and proteomics to identify and validate in vivo substrates of bone morphogenetic protein 1/tolloid-like metalloproteinases (2003) Mol Cell Biol., 23 (13), pp. 4428-4438
Kessler, E., Takahara, K., Biniaminov, L., Brusel, M., Greenspan, D.S., Bone morphogenetic protein-1: The type i procollagen C-proteinase (1996) Science., 271 (5247), pp. 360-362
Li, S.W., Sieron, A.L., Fertala, A., Hojima, Y., Arnold, W.V., Prockop, D.J., The C-proteinase that processes procollagens to fibrillar collagens is identical to the protein previously identified as bone morphogenic protein-1 (1996) Proc Natl Acad Sci USA., 93 (10), pp. 5127-5130
Muir, A., Greenspan, D.S., Metalloproteinases in Drosophila to humans that are central players in developmental processes (2011) J Biol Chem., 286 (49), pp. 41905-41911
Imamura, Y., Steiglitz, B.M., Greenspan, D.S., Bone morphogenetic protein-1 processes the NH2-terminal propeptide, and a furin-like proprotein convertase processes the COOH-terminal propeptide of pro-alpha1(V) collagen (1998) J Biol Chem., 273 (42), pp. 27511-27517
Linsenmayer, T.F., Gibney, E., Igoe, F., Type v collagen: Molecular structure and fibrillar organization of the chicken alpha 1(V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis (1993) J Cell Biol., 121 (5), pp. 1181-1189
Mendler, M., Eich-Bender, S.G., Vaughan, L., Winterhalter, K.H., Bruckner, P., Cartilage contains mixed fibrils of collagen types II, IX, and XI (1989) J Cell Biol., 108 (1), pp. 191-197
Uzel, M.I., Scott, I.C., Babakhanlou-Chase, H., Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures (2001) J Biol Chem., 276 (25), pp. 22537-22543
Von, M.Z., Fisher, L.W., Decorin is processed by three isoforms of bone morphogenetic protein-1 (BMP1) (2010) Biochem Biophys Res Commun., 391 (3), pp. 1374-1378
Scott, I.C., Imamura, Y., Pappano, W.N., Bone morphogenetic protein-1 processes probiglycan (2000) J Biol Chem., 275 (39), pp. 30504-30511
Nuytinck, L., Narcisi, P., Nicholls, A., Renard, J.P., Pope, F.M., De Paepe, A., Detection and characterisation of an overmodified type III collagen by analysis of non-cutaneous connective tissues in a patient with Ehlers-Danlos syndrome IV (1992) J Med Genet., 29 (6), pp. 375-380
Cabral, W.A., Makareeva, E., Colige, A., Mutations near amino end of alpha1(I) collagen cause combined osteogenesis imperfecta/Ehlers-Danlos syndrome by interference with N-propeptide processing (2005) J Biol Chem., 280 (19), pp. 19259-19269
Schindelin, J., Arganda-Carreras, I., Frise, E., Fiji: An open-source platform for biological-image analysis (2012) Nat Methods., 9 (7), pp. 676-682
Fisher, L.W., Stubbs, J.T., Young, M.F., Antisera and cDNA probes to human and certain animal model bone matrix noncollagenous proteins (1995) Acta Orthop Scand Suppl., 266, pp. 61-65
Malfait, F., Coucke, P., Symoens, S., Loeys, B., Nuytinck, L., De Paepe, A., The molecular basis of classic Ehlers-Danlos syndrome: A comprehensive study of biochemical and molecular findings in 48 unrelated patients (2005) Hum Mutat., 25 (1), pp. 28-37
Mochida, Y., Parisuthiman, D., Pornprasertsuk-Damrongsri, S., Decorin modulates collagen matrix assembly and mineralization (2009) Matrix Biol., 28 (1), pp. 44-52
Danielson, K.G., Baribault, H., Holmes, D.F., Graham, H., Kadler, K.E., Iozzo, R.V., Targeted disruption of decorin leads to abnormal collagen fibril morphology and skin fragility (1997) J Cell Biol., 136 (3), pp. 729-743
Willaert, A., Malfait, F., Symoens, S., Recessive osteogenesis imperfecta caused by LEPRE1 mutations: Clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation (2009) J Med Genet., 46 (4), pp. 233-241
Hartigan, N., Garrigue-Antar, L., Kadler, K.E., Bone morphogenetic protein-1 (BMP-1). Identification of the minimal domain structure for procollagen C-proteinase activity (2003) J Biol Chem., 278 (20), pp. 18045-18049
Hoyer-Kuhn, H., Semler, O., Schoenau, E., Roschger, P., Klaushofer, K., Rauch, F., Hyperosteoidosis and hypermineralization in the same bone: Bone tissue analyses in a boy with a homozygous BMP1 mutation (2013) Calcif Tissue Int., 93 (6), pp. 565-570
Muir, A.M., Ren, Y., Butz, D.H., Induced ablation of Bmp1 and Tll1 produces osteogenesis imperfecta in mice (2014) Hum Mol Genet., 23 (12), pp. 3085-3101
Pace, J.M., Chitayat, D., Atkinson, M., Wilcox, W.R., Schwarze, U., Byers, P.H., A single amino acid substitution (D1441Y) in the carboxyl-terminal propeptide of the proalpha1(I) chain of type i collagen results in a lethal variant of osteogenesis imperfecta with features of dense bone diseases (2002) J Med Genet., 39 (1), pp. 23-29
Lindahl, K., Barnes, A.M., Fratzl-Zelman, N., COL1 C-propeptide cleavage site mutations cause high bone mass osteogenesis imperfecta (2011) Hum Mutat., 32 (6), pp. 598-609
Wu, C.H., Donovan, C.B., Wu, G.Y., Evidence for pretranslational regulation of collagen synthesis by procollagen propeptides (1986) J Biol Chem., 261 (23), pp. 10482-10484
Mizuno, M., Fujisawa, R., Kuboki, Y., The effect of carboxyl-terminal propeptide of type i collagen (c-propeptide) on collagen synthesis of preosteoblasts and osteoblasts (2000) Calcif Tissue Int., 67 (5), pp. 391-399
Mizuno, M., Fujisawa, R., Kuboki, Y., Carboxyl-terminal propeptide of type i collagen (c-propeptide) modulates the action of TGF-beta on MC3T3-E1 osteoblastic cells (2000) FEBS Lett., 479 (3), pp. 123-126
Canty, E.G., Kadler, K.E., Procollagen trafficking, processing and fibrillogenesis (2005) J Cell Sci., 118, pp. 1341-1353
Symoens, S., Renard, M., Bonod-Bidaud, C., Identification of binding partners interacting with the α1-N-propeptide of type v collagen (2011) Biochem J., 433 (2), pp. 371-381
Ge, G., Seo, N.-S., Liang, X., Hopkins, D.R., Höök, M., Greenspan, D.S., Bone morphogenetic protein-1/tolloid-related metalloproteinases process osteoglycin and enhance its ability to regulate collagen fibrillogenesis (2004) J Biol Chem., 279 (40), pp. 41626-41633
Grafe, I., Yang, T., Alexander, S., Excessive transforming growth factor-β signaling is a common mechanism in osteogenesis imperfecta (2014) Nat Med., 20 (6), pp. 670-675
Ge, G., Greenspan, D.S., BMP1 controls TGFbeta1 activation via cleavage of latent TGFbeta-binding protein (2006) J Cell Biol., 175 (1), pp. 111-120