{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T04:17:46Z","timestamp":1778991466558,"version":"3.51.4"},"reference-count":33,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BePharBel Manufacturing\u2014R\u00e9gion Wallonne","award":["7437"],"award-info":[{"award-number":["7437"]}]},{"name":"Association Francophone Belge de l\u2019Ost\u00e9ogen\u00e8se Imparfaite (AFBOI)","award":["7437"],"award-info":[{"award-number":["7437"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteogenesis imperfecta (OI) is a rare congenital bone dysplasia generally caused by a mutation of one of the type I collagen genes and characterized by low bone mass, numerous fractures, and bone deformities. The collagen organization and osteocyte lacuna arrangement were investigated in the long bones of 17-week-old wildtype (WT, n = 17) and osteogenesis imperfecta mice (OIM, n = 16) that is a validated model of severe human OI in order to assess their possible role in bone fragility. Fractures were counted after in vivo scanning at weeks 5, 11, and 17. Humerus, femur, and tibia diaphyses from both groups were analyzed ex vivo with pQCT, polarized and ordinary light histology, and Nano-CT. The fractures observed in the OIM were more numerous in the humerus and femur than in the tibia, whereas the quantitative bone parameters were altered in different ways among these bones. Collagen fiber organization appeared disrupted, with a lower birefringence in OIM than WT bones, whereas the osteocyte lacunae were more numerous, more spherical, and not aligned in a lamellar pattern. These modifications, which are typical of immature and less mechanically competent bone, attest to the reciprocal alteration of collagen matrix and osteocyte lacuna organization in the OIM, thereby contributing to bone fragility.<\/jats:p>","DOI":"10.3390\/ijms242317010","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T09:39:12Z","timestamp":1701337152000},"page":"17010","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Col1A-2 Mutation in Osteogenesis Imperfecta Mice Contributes to Long Bone Fragility by Modifying Cell-Matrix Organization"],"prefix":"10.3390","volume":"24","author":[{"given":"Gr\u00e9goire","family":"Andr\u00e9","sequence":"first","affiliation":[{"name":"Pole of Morphology, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1510-3515","authenticated-orcid":false,"given":"Antoine","family":"Chretien","sequence":"additional","affiliation":[{"name":"Pole of Morphology, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Demoulin","sequence":"additional","affiliation":[{"name":"Pole of Morphology, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e9lanie","family":"Beersaerts","sequence":"additional","affiliation":[{"name":"Pole of Morphology, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre-Louis","family":"Docquier","sequence":"additional","affiliation":[{"name":"Neuromusculoskeletal Lab, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0468-7076","authenticated-orcid":false,"given":"Catherine","family":"Behets","sequence":"additional","affiliation":[{"name":"Pole of Morphology, Institute of Experimental and Clinical Research, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,30]]},"reference":[{"key":"ref_1","unstructured":"Feingold, K.R., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., Dungan, K., and Hofland, J. (2023, August 03). Osteogenesis Imperfecta, Endotext, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK279109\/."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.trsl.2016.11.005","article-title":"Osteogenesis imperfecta: New genes reveal novel mechanisms in bone dysplasia","volume":"181","author":"Kang","year":"2017","journal-title":"Transl. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1136\/jmg.16.2.101","article-title":"Genetic heterogeneity in osteogenesis imperfecta","volume":"16","author":"Sillence","year":"1979","journal-title":"J. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1016\/S0140-6736(15)00728-X","article-title":"Osteogenesis imperfecta","volume":"387","author":"Forlino","year":"2016","journal-title":"Lancet"},{"key":"ref_5","unstructured":"Shapiro, J., Kassim, J., and Sponseller, P. (2013). Osteogenesis Imperfecta: A Translational Approach to Brittle Bone Disease, Elsevier Inc.. [1st ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.bone.2019.04.011","article-title":"Sclerostin antibody reduces long bone fractures in the oim\/oim model of osteogenesis imperfecta","volume":"124","author":"Cardinal","year":"2019","journal-title":"Bone"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/jbmr.320","article-title":"The amazing osteocyte","volume":"26","author":"Bonewald","year":"2011","journal-title":"J. Bone Miner. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bone.2019.01.025","article-title":"Changes in the osteocyte lacunocanalicular network with aging","volume":"122","author":"Dallas","year":"2019","journal-title":"Bone"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1126\/science.7684161","article-title":"Mechanotransduction across the cell surface and through the cytoskeleton","volume":"260","author":"Wang","year":"1993","journal-title":"Science"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1242\/jcs.01581","article-title":"The metalloproteinase MT1-MMP is required for normal development and maintenance of osteocyte processes in bone","volume":"118","author":"Holmbeck","year":"2005","journal-title":"J. Cell Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4539","DOI":"10.1128\/MCB.02120-05","article-title":"E11\/gp38 Selective Expression in Osteocytes: Regulation by Mechanical Strain and Role in Dendrite Elongation","volume":"26","author":"Zhang","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"578477","DOI":"10.3389\/fendo.2020.578477","article-title":"Control of Bone Matrix Properties by Osteocytes","volume":"11","author":"Creecy","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s00795-015-0099-y","article-title":"The osteocyte plays multiple roles in bone remodeling and mineral homeostasis","volume":"48","author":"Chen","year":"2015","journal-title":"Med. Mol. Morphol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1016\/j.jbiomech.2008.01.031","article-title":"Round versus flat: Bone cell morphology, elasticity, and mechanosensing","volume":"41","author":"Bacabac","year":"2008","journal-title":"J. Biomech."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1461","DOI":"10.1002\/jbmr.3730","article-title":"Mechanical Competence and Bone Quality Develop During Skeletal Growth","volume":"34","author":"Zimmermann","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.bone.2010.07.026","article-title":"Towards quantitative 3D imaging of the osteocyte lacuno-canalicular network","volume":"47","author":"Schneider","year":"2010","journal-title":"Bone"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1073\/pnas.90.5.1701","article-title":"Defective pro alpha 2(I) collagen synthesis in a recessive mutation in mice: A model of human osteogenesis imperfecta","volume":"90","author":"Chipman","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1007\/s00223-019-00655-5","article-title":"Sclerostin-Antibody Treatment Decreases Fracture Rates in Axial Skeleton and Improves the Skeletal Phenotype in Growing oim\/oim Mice","volume":"106","author":"Cardinal","year":"2020","journal-title":"Calcif. Tissue Int."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shi, C., Sun, B., Ma, C., Wu, H., Chen, R., He, H., and Zhang, Y. (2021). Comparable Effects of Strontium Ranelate and Alendronate Treatment on Fracture Reduction in a Mouse Model of Osteogenesis Imperfecta. BioMed Res. Int., 2021.","DOI":"10.1155\/2021\/4243105"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3109\/03008200903108472","article-title":"RANKL inhibition improves bone properties in a mouse model of osteogenesis imperfecta","volume":"51","author":"Bargman","year":"2010","journal-title":"Connect. Tissue Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1136\/adc.80.6.524","article-title":"Anthropometry of patients with osteogenesis imperfecta","volume":"80","author":"Lund","year":"1999","journal-title":"Arch. Dis. Child."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chretien, A., Couchot, M., Mabilleau, G., and Behets, C. (2022). Biomechanical, Microstructural and Material Properties of Tendon and Bone in the Young Oim Mice Model of Osteogenesis Imperfecta. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179928"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1016\/S0021-9290(96)80002-9","article-title":"Collagen Fiber organization is related to mechanical properties and remodeling in equine bone. A comparsion of two methods","volume":"29","author":"Martin","year":"1996","journal-title":"J. Biomech."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"100734","DOI":"10.1016\/j.bonr.2020.100734","article-title":"Histopathology of osteogenesis imperfecta bone. Supramolecular assessment of cells and matrices in the context of woven and lamellar bone formation using light, polarization and ultrastructural microscopy","volume":"14","author":"Shapiro","year":"2021","journal-title":"Bone Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1002\/jbmr.2172","article-title":"How Tough Is Brittle Bone? Investigating Osteogenesis Imperfecta in Mouse Bone","volume":"29","author":"Carriero","year":"2014","journal-title":"J. Bone Miner. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.bone.2012.03.007","article-title":"Ultra-structural defects cause low bone matrix stiffness despite high mineralization in osteogenesis imperfecta mice","volume":"50","author":"Vanleene","year":"2012","journal-title":"Bone"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.jsb.2010.11.014","article-title":"The organization of the osteocyte network mirrors the extracellular matrix orientation in bone","volume":"173","author":"Kerschnitzki","year":"2011","journal-title":"J. Struct. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1002\/jbmr.3180","article-title":"Hypermineralization and high osteocyte lacunar density in osteogenesis imperfecta type V bone indicate exuberant primary bone formation","volume":"32","author":"Blouin","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Schemenz, V., Gjardy, A., Chamasemani, F.F., Roschger, A., Roschger, P., Zaslansky, P., Helfen, L., Burghammer, M., Fratzl, P., and Weinkamer, R. (2020). Heterogeneity of the osteocyte lacuno-canalicular network architecture and material characteristics across different tissue types in healing bone. J. Struct. Biol., 212.","DOI":"10.1016\/j.jsb.2020.107616"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.bone.2013.12.020","article-title":"Altered lacunar and vascular porosity in osteogenesis imperfecta mouse bone as revealed by synchrotron tomography contributes to bone fragility","volume":"61","author":"Carriero","year":"2014","journal-title":"Bone"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s11914-023-00792-9","article-title":"Influence of Osteocyte Lacunar-Canalicular Morphology and Network Architecture on Osteocyte Mechanosensitivity","volume":"21","author":"Sang","year":"2023","journal-title":"Curr. Osteoporos. Rep."},{"key":"ref_32","unstructured":"Maes, A. (2023, October 06). Contrast-Team\/Histogram-Windowing: Initial Release. Zenodo. Available online: https:\/\/zenodo.org\/records\/7034265."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6207","DOI":"10.1038\/s41467-022-34048-4","article-title":"Cryogenic contrast-enhanced microCT enables nondestructive 3D quantitative histopathology of soft biological tissues","volume":"13","author":"Maes","year":"2022","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/17010\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:35:12Z","timestamp":1760132112000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/23\/17010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,30]]},"references-count":33,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242317010"],"URL":"https:\/\/doi.org\/10.3390\/ijms242317010","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,30]]}}}