Differential expression of both extracellular and intracellular proteins is involved in the lethal or nonlethal phenotypic variation of BrtlIV, a murine model for osteogenesis imperfecta
Abstract
This study used proteomic and transcriptomic techniques to understand the molecular basis of the phenotypic variability in the bone disorder osteogenesis imperfecta (OI). Calvarial bone mRNA expression was evaluated by microarray, real‐time, and comparative RT‐PCR and the bone proteome profile was analyzed by 2‐DE, MS, and immunoblotting in the OI murine model BrtlIV, which has either a moderate or a lethal OI outcome. Differential expression analysis showed significant changes for eight proteins. The expression of the ER stress‐related protein Gadd153 was increased in lethal mice, whereas expression of the chaperone αB crystallin was increased in nonlethal mice, suggesting that the intracellular machinery is involved in the modulation of the OI phenotype. Furthermore, in lethal BrtlIV, the increased expression of the cartilaginous proteins Prelp, Bmp6, and Bmp7 and the lower expression of the bone matrix proteins matrilin 4, microfibril‐associated glycoprotein 2, and thrombospondin 3 revealed that both a delay in skeletal development and an alteration in extracellular matrix composition influence OI outcomes. Differentially expressed proteins identified in this model offer a starting point for elucidating the molecular basis of phenotypic variability, a characteristic common to many genetic disorders. The first reference 2‐DE map for murine calvarial tissue is also reported.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Procollagen misfolding caused by mutations within the triple helix domain likely does not activate UPR, but rather leads to the accumulation of insoluble procollagen aggregates that could be eliminated by autophagy.
“it is likely that procollagen misfolding caused by mutations within the triple helix domain does not activate UPR [60,63], but rather leads to the accumulation of insoluble procollagen aggregates that could be eliminated by autophagy [64]”
Cites
A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels
Oakley, B. R., Kirsch, D. R., & Morris, N. R. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90470-4 · Cited by 3,248 · see citing works
Genetic heterogeneity in osteogenesis imperfecta.
Sillence, D. O., Senn, A., & Danks, D. M. (1979) · Journal of Medical Genetics · doi:10.1136/jmg.16.2.101 · Cited by 2,244 · see citing works
COLLAGENS: Molecular Biology, Diseases, and Potentials for Therapy
Prockop, D. J., & Kivirikko, K. I. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.002155 · Cited by 1,625 · see citing works
Nelson's Textbook of Pediatrics
Behrman (2000) · Cited by 771 · see citing works
Marini, J. C., Forlino, A., Cabral, W. A., Barnes, A. M., Antonio, J. D. S., Milgrom, S. A., Hyland, J. C., Körkkö, J., Prockop, D. J., Paepe, A. D., et al. (2006) · Human Mutation · doi:10.1002/humu.20429 · Cited by 764 · see citing works
Self-citationThe molecular structure of collagen
Rich, A., & Crick, F. H. C. (1961) · Journal of Molecular Biology · doi:10.1016/s0022-2836(61)80016-8 · Cited by 755 · see citing works
Hellman, U., Wernstedt, C., Góñez, L. J., & Heldin, C. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1070 · Cited by 753 · see citing works
Molecular Structure of Collagen
Ramachandran, G. N. (1963) · International review of connective tissue research · doi:10.1016/b978-1-4831-6755-8.50009-7 · Cited by 719 · see citing works
Analysis of Human Genetic Linkage
Read, A. (1992) · Journal of Medical Genetics · doi:10.1136/jmg.29.9.680 · Cited by 629 · see citing works
Small Stress Proteins as Novel Regulators of Apoptosis
Mehlen, P., Schulze‐Osthoff, K., & Arrigo, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.28.16510 · Cited by 604 · see citing works
Osteogenesis imperfecta: translation of mutation to phenotype.
Byers, P. H., Wallis, G. A., & Willing, M. C. (1991) · Journal of Medical Genetics · doi:10.1136/jmg.28.7.433 · Cited by 326 · see citing works
Chain conformation in the collagen molecule
Fraser, R., MacRae, T. P., & Suzuki, E. (1979) · Journal of Molecular Biology · doi:10.1016/0022-2836(79)90507-2 · Cited by 322 · see citing works
The human type I collagen mutation database
Dalgleish, R. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.1.181 · Cited by 315 · see citing works
Hochstrasser, D. F., Patchornik, A., & Merril, C. R. (1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90208-4 · Cited by 306 · see citing works
Principles and Practice of Medical Genetics.
Erickson, R. P. (1991) · Annals of Internal Medicine · doi:10.7326/0003-4819-114-9-817_2 · Cited by 291 · see citing works
The Human Collagen Mutation Database 1998
Dalgleish, R. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.1.253 · Cited by 219 · see citing works
Bjellqvist, B., Sanchez, J., Pasquali, C., et al. (1993) · Electrophoresis · doi:10.1002/elps.11501401212 · Cited by 188 · see citing works
Forlino, A., Porter, F. D., Lee, E. J., Westphal, H., & Marini, J. C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.53.37923 · Cited by 159 · see citing works
Self-citationKozloff, K. M., Carden, A., Bergwitz, C., et al. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040111 · Cited by 143 · see citing works
Chávez-Zobel, A. T. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg173 · Cited by 141 · see citing works
Lamandé, S. R., Chessler, S. D., Golub, S. B., Byers, P. H., Chan, C., Cole, W. G., Sillence, D. O., & Bateman, J. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.15.8642 · Cited by 135 · see citing works
Protein identification in DNA databases by peptide mass fingerprinting
James, P., Quadroni, M., Carafoli, E., et al. (1994) · Protein Science · doi:10.1002/pro.5560030822 · Cited by 131 · see citing works
Görg, A., Postel, W., Günther, S., Weser, J., Strahler, J. R., Hanash, S., Somerlot, L., & Kuick, R. D. (1988) · Electrophoresis · doi:10.1002/elps.1150090108 · Cited by 99 · see citing works
Gibson, M. A., Finnis, M., Kumaratilake, J., et al. (1998) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215549804600802 · Cited by 98 · see citing works
Kubota, K., Wakabayashi, K., & Matsuoka, T. (2003) · PROTEOMICS · doi:10.1002/pmic.200300410 · Cited by 84 · see citing works
Proteasomal Degradation of Unassembled Mutant Type I Collagen Pro-α1(I) Chains
Fitzgerald, J., Lamandé, S. R., & Bateman, J. F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.39.27392 · Cited by 81 · see citing works
Strategic Attack on Host Cell Gene Expression during Adenovirus Infection
Zhao, H., Granberg, F., Elfineh, L., Pettersson, U., & Svensson, C. (2003) · Journal of Virology · doi:10.1128/jvi.77.20.11006-11015.2003 · Cited by 80 · see citing works
Hankenson, K. D., Hormuzdi, S. G., Meganck, J. A., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.13.5599-5606.2005 · Cited by 77 · see citing works
Expression of matrilins during maturation of mouse skeletal tissues
Klatt, A. R., Paulsson, M., & Wagener, R. (2002) · Matrix Biology · doi:10.1016/s0945-053x(02)00006-9 · Cited by 74 · see citing works
Roman‐Roman, S., Garcia, T., Jackson, A. M., Theilhaber, J., Rawadi, G., Connolly, T. M., Spinella-Jaegle, S., Kawai, S., Courtois, B., Bushnell, S., et al. (2003) · Bone · doi:10.1016/s8756-3282(03)00052-8 · Cited by 70 · see citing works
Interaction between αB-crystallin and the human 20S proteasomal subunit C8/α7
Boelens, W. C., Croes, Y., & JONG, W. W. D. (2001) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(00)00243-0 · Cited by 69 · see citing works
Radiographic Manifestations of Congenital Anomalies of the Skull
Kaplan, S. B., Kemp, S. S., & Oh, K. S. (1991) · Radiologic Clinics of North America · doi:10.1016/s0033-8389(22)02693-8 · Cited by 65 · see citing works
Anthropometry of patients with osteogenesis imperfecta
Lund, A. M., Müller, J., & Skovby, F. (1999) · Archives of Disease in Childhood · doi:10.1136/adc.80.6.524 · Cited by 63 · see citing works
Osteogenesis Imperfecta: Prospects for Molecular Therapeutics
Forlino, A., & Marini, J. C. (2000) · Molecular Genetics and Metabolism · doi:10.1006/mgme.2000.3039 · Cited by 63 · see citing works
Self-citationCalcyclin, a Ca2+ Ion-binding Protein, Contributes to the Anabolic Effects of Simvastatin on Bone
Hwang, R., Lee, E. J., Kim, M. H., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312771200 · Cited by 60 · see citing works
Cabral, W. A., & Marini, J. C. (2004) · The American Journal of Human Genetics · doi:10.1086/383252 · Cited by 56 · see citing works
Self-citationIdentification of cystic fibrosis mutations in the United Arab Emirates
Frossard, P. M., Girodon, E., Dawson, K. P., Ghanem, N., Plassa, F., Lestringant, G. G., & Goossens, M. (1998) · Human Mutation · doi:10.1002/(sici)1098-1004(1998)11:5 · Cited by 50 · see citing works
Byers, P. H., & Cole, W. G. (2002) · doi:10.1002/0471221929.ch8 · Cited by 50 · see citing works
Pereira, R., Halford, K. W., Sokolov, B. P., et al. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117161 · Cited by 49 · see citing works
Pastorelli, R., Carpi, D., Airoldi, L., Chiabrando, C., Bagnati, R., Fanelli, R., Moverare, S., & Ohlsson, C. (2005) · PROTEOMICS · doi:10.1002/pmic.200401325 · Cited by 38 · see citing works
Kuznetsova, N. V., Forlino, A., Cabral, W. A., Marini, J. C., & Leikin, S. (2004) · Matrix Biology · doi:10.1016/j.matbio.2004.03.002 · Cited by 33 · see citing works
Self-citationProteomic analysis of cartilage‐ and bone‐associated samples
Lammi, M. J., Häyrinen, J., & Mahonen, A. (2006) · Electrophoresis · doi:10.1002/elps.200600004 · Cited by 28 · see citing works
Functional proteome of bones in rats with osteoporosis following ovariectomy
Fan, Y., Liu, J., Wang, S., Wang, H., Shi, F., Xiong, L., He, W., & Peng, X. (2005) · Life Sciences · doi:10.1016/j.lfs.2004.10.059 · Cited by 27 · see citing works
Extracellular matrix receptor and platelet antigens on osteoclasts and foreign body giant cells
Quinn, J. M. W., Athanasou, N. A., & McGee, J. O. (1991) · Histochemistry · doi:10.1007/bf00315989 · Cited by 25 · see citing works
Elucidation of CPX‐1 involvement in RANKL‐induced osteoclastogenesis by a proteomics approach
Chang, E., Kwak, H. B., Kim, H., Park, J., Lee, Z. H., & Kim, H.-H. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00338-2 · Cited by 22 · see citing works
The Bone Cell Biology of Osteogenesis Imperfecta
Fedarko, N. S., Vetter, U. K., & Robey, P. G. (1995) · Connective Tissue Research · doi:10.3109/03008209509010821 · Cited by 11 · see citing works
Localization of platelet antigens and fibrinogen on osteoclasts
Athanasou, N. A., Quinn, J. M. W., Heryet, A. R., & McGee, J. O. (1988) · Journal of Cell Science · doi:10.1242/jcs.89.1.115 · Cited by 8 · see citing works
Disorders of Intracellular Protein Trafficking in Human Disease
Delahunty, M. D., & Bonifacino, J. S. (1995) · Connective Tissue Research · doi:10.3109/03008209509010824 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Marini, J. C., Forlino, A., Bächinger, H. P., Bishop, N. J., Byers, P. H., Paepe, A. D., Fassier, F., Fratzl-Zelman, N., Kozloff, K. M., Krakow, D., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.52 · Cited by 842 · see citing works
Self-citationGenetic diseases of connective tissues: cellular and extracellular effects of ECM mutations
Bateman, J. F., Boot-Handford, R. P., & Lamandé, S. R. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2520 · Cited by 338 · see citing works
The unfolded protein response and its relevance to connective tissue diseases
Boot-Handford, R. P., & Briggs, M. D. (2010) · Cell and Tissue Research · doi:10.1007/s00441-009-0877-8 · Cited by 143 · see citing works
Chiarelli, N., Carini, G., Zoppi, N., Ritelli, M., & Colombi, M. (2018) · PLOS ONE · doi:10.1371/journal.pone.0191220 · Cited by 45 · see citing works
- Authors
- Forlino, A., Tani, C., Rossi, A., Lupi, A., Campari, E., Gualeni, B., Bianchi, L., Armini, A., Cetta, G., Bini, L., & Marini, J. C.
- Affiliations
- University of Pavia (IT)
- University of Siena (IT)
- National Institutes of Health (US)
- Corresponding author
- Forlino, Antonella
- Venue
- PROTEOMICS
- Publisher
- Wiley
- Published
- 2007-05-22
- Volume
- 7
- Issue
- 11
- Pages
- 1877-1891
- ISSN
- 1615-9853 (ISSN-L)
- 1615-9861
- OpenAlex
- W2007055861
- Cited by
- 54
- References
- 48
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 6 · 2012: 4
- FWCI
- 2.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- PROTEOMICS (publishedVersion)
- PubMed (publishedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
- Keywords
- osteogenesis imperfecta, phenotypic variability, calvarial bone, differentially expressed proteins, GADD153, endoplasmic reticulum stress, alphaB-crystallin, molecular chaperones, BMP6, BMP-7, PRELP, extracellular matrix, skeletal development
- MeSH terms
- Animals, Bone and Bones, Disease Models, Animal, Genes, Lethal, Genetic Markers, Osteogenesis Imperfecta, Phenotype, Genetic Variation, Blotting, Western, Electrophoresis, Gel, Two-Dimensional, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Amino Acid Substitution, Reverse Transcriptase Polymerase Chain Reaction, Collagen Type I, Microarray Analysis, Mice, Transcription Factor CHOP
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review