{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T04:11:20Z","timestamp":1793851880267,"version":"4.6.1"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100000341","name":"Arthritis Research UK","doi-asserted-by":"publisher","award":["20581"],"award-info":[{"award-number":["20581"]}],"id":[{"id":"10.13039\/501100000341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R025673\/1"],"award-info":[{"award-number":["MR\/R025673\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"RCUK | Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/I02249X\/1"],"award-info":[{"award-number":["EP\/I02249X\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"RCUK | Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/M009688\/1"],"award-info":[{"award-number":["EP\/M009688\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Biomed Eng"],"DOI":"10.1038\/s41551-019-0477-1","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T12:02:50Z","timestamp":1574683370000},"page":"343-354","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["In situ characterization of nanoscale strains in loaded whole joints via synchrotron X-ray tomography"],"prefix":"10.1038","volume":"4","author":[{"given":"Kamel","family":"Madi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine A.","family":"Staines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6870-259X","authenticated-orcid":false,"given":"Brian K.","family":"Bay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7941-3104","authenticated-orcid":false,"given":"Behzad","family":"Javaheri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Bodey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Cartmell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3861-998X","authenticated-orcid":false,"given":"Andrew A.","family":"Pitsillides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3898-8881","authenticated-orcid":false,"given":"Peter D.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,25]]},"reference":[{"key":"477_CR1","doi-asserted-by":"publisher","first-page":"e329","DOI":"10.1371\/journal.pbio.0020329","volume":"2","author":"W Denk","year":"2004","unstructured":"Denk, W. & Horstmann, H. Serial block-face scanning electron microscopy to reconstruct three-dimensional tissue nanostructure. PLoS Biol. 2, e329 (2004).","journal-title":"PLoS Biol."},{"key":"477_CR2","doi-asserted-by":"publisher","first-page":"20160088","DOI":"10.1098\/rsif.2016.0088","volume":"13","author":"M Georgiadis","year":"2016","unstructured":"Georgiadis, M., Mueller, R. & Schneider, P. Techniques to assess bone ultrastructure organization: orientation and arrangement of mineralized collagen fibrils. J. R. Soc. Interface 13, 20160088 (2016).","journal-title":"J. R. Soc. Interface"},{"key":"477_CR3","doi-asserted-by":"crossref","unstructured":"Pabisch, S., Wagermaier, W., Zander, T., Li, C. & Fratzl, P. in Methods in Enzymology Vol. 532 (ed. De Yoreo, J.) 391\u2013413 (Elsevier, 2013).","DOI":"10.1016\/B978-0-12-416617-2.00018-7"},{"key":"477_CR4","doi-asserted-by":"publisher","first-page":"185705","DOI":"10.1088\/0957-4484\/25\/18\/185705","volume":"25","author":"F-Y Zhu","year":"2014","unstructured":"Zhu, F.-Y. et al. 3D nanostructure reconstruction based on the SEM imaging principle, and applications. Nanotechnology 25, 185705 (2014).","journal-title":"Nanotechnology"},{"key":"477_CR5","doi-asserted-by":"publisher","first-page":"17741","DOI":"10.1073\/pnas.0604237103","volume":"103","author":"HS Gupta","year":"2006","unstructured":"Gupta, H. S. et al. Cooperative deformation of mineral and collagen in bone at the nanoscale. Proc. Natl Acad. Sci. USA 103, 17741\u201317746 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"477_CR6","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1016\/j.jbiomech.2008.01.005","volume":"41","author":"S Tadano","year":"2008","unstructured":"Tadano, S., Giri, B., Sato, T., Fujisaki, K. & Todoh, M. Estimating nanoscale deformation in bone by X-ray diffraction imaging method. J. Biomech. 41, 945\u2013952 (2008).","journal-title":"J. Biomech."},{"key":"477_CR7","doi-asserted-by":"publisher","first-page":"9001","DOI":"10.1073\/pnas.0502718103","volume":"103","author":"JP Orgel","year":"2006","unstructured":"Orgel, J. P., Irving, T. C., Miller, A. & Wess, T. J. Microfibrillar structure of type I collagen in situ. Proc. Natl Acad. Sci. USA 103, 9001\u20139005 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"477_CR8","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1021\/nl103943u","volume":"11","author":"A Gautieri","year":"2011","unstructured":"Gautieri, A., Vesentini, S., Redaelli, A. & Buehler, M. J. Hierarchical structure and nanomechanics of collagen microfibrils from the atomistic scale up. Nano Lett. 11, 757\u2013766 (2011).","journal-title":"Nano Lett."},{"key":"477_CR9","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1038\/nature09419","volume":"467","author":"M Dierolf","year":"2010","unstructured":"Dierolf, M. et al. Ptychographic X-ray computed tomography at the nanoscale. Nature 467, 436\u2013439 (2010).","journal-title":"Nature"},{"key":"477_CR10","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.joms.2006.10.025","volume":"65","author":"LA Giannuzzi","year":"2007","unstructured":"Giannuzzi, L. A., Phifer, D., Giannuzzi, N. J. & Capuano, M. J. Two-dimensional and 3-dimensional analysis of bone\/dental implant interfaces with the use of focused ion beam and electron microscopy. J. Oral Maxillofac. Surg. 65, 737\u2013747 (2007).","journal-title":"J. Oral Maxillofac. Surg."},{"key":"477_CR11","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.bone.2011.04.005","volume":"49","author":"P Schneider","year":"2011","unstructured":"Schneider, P., Meier, M., Wepf, R. & M\u00fcller, R. Serial FIB\/SEM imaging for quantitative 3D assessment of the osteocyte lacuno-canalicular network. Bone 49, 304\u2013311 (2011).","journal-title":"Bone"},{"key":"477_CR12","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1002\/(SICI)1097-0029(19960201)33:2<92::AID-JEMT2>3.0.CO;2-0","volume":"33","author":"A Boyde","year":"1996","unstructured":"Boyde, A. & Jones, S. J. Scanning electron microscopy of bone: instrument, specimen, and issues. Microsc. Res. Tech. 33, 92\u2013120 (1996).","journal-title":"Microsc. Res. Tech."},{"key":"477_CR13","doi-asserted-by":"publisher","first-page":"e12796","DOI":"10.1371\/journal.pone.0012796","volume":"5","author":"MJ Song","year":"2010","unstructured":"Song, M. J., Dean, D. & Tate, M. L. K. In situ spatiotemporal mapping of flow fields around seeded stem cells at the subcellular length scale. PLoS ONE 5, e12796 (2010).","journal-title":"PLoS ONE"},{"key":"477_CR14","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1115\/1.1824127","volume":"126","author":"BA Roeder","year":"2004","unstructured":"Roeder, B. A., Kokini, K., Robinson, J. P. & Voytik-Harbin, S. L. Local, three-dimensional strain measurements within largely deformed extracellular matrix constructs. J. Biomech. Eng. 126, 699\u2013708 (2004).","journal-title":"J. Biomech. Eng."},{"key":"477_CR15","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.jbiomech.2009.10.042","volume":"43","author":"P Sztefek","year":"2010","unstructured":"Sztefek, P. et al. Using digital image correlation to determine bone surface strains during loading and after adaptation of the mouse tibia. J. Biomech. 43, 599\u2013605 (2010).","journal-title":"J. Biomech."},{"key":"477_CR16","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.bone.2005.09.017","volume":"38","author":"T Hoc","year":"2006","unstructured":"Hoc, T. et al. Effect of microstructure on the mechanical properties of Haversian cortical bone. Bone 38, 466\u2013474 (2006).","journal-title":"Bone"},{"key":"477_CR17","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1002\/jor.1100130214","volume":"13","author":"BK Bay","year":"1995","unstructured":"Bay, B. K. Texture correlation: a method for the measurement of detailed strain distributions within trabecular bone. J. Orthop. Res. 13, 258\u2013267 (1995).","journal-title":"J. Orthop. Res."},{"key":"477_CR18","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1016\/j.jbiomech.2005.04.032","volume":"39","author":"DP Nicolella","year":"2006","unstructured":"Nicolella, D. P., Moravits, D. E., Gale, A. M., Bonewald, L. F. & Lankford, J. Osteocyte lacunae tissue strain in cortical bone. J. Biomech. 39, 1735\u20131743 (2006).","journal-title":"J. Biomech."},{"key":"477_CR19","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1016\/j.jmbbm.2012.08.016","volume":"17","author":"OL Katsamenis","year":"2013","unstructured":"Katsamenis, O. L., Chong, H. M., Andriotis, O. G. & Thurner, P. J. Load-bearing in cortical bone microstructure: Selective stiffening and heterogeneous strain distribution at the lamellar level. J. Mech. Behav. Biomed. Mater. 17, 152\u2013165 (2013).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"477_CR20","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/nmat1911","volume":"6","author":"K Tai","year":"2007","unstructured":"Tai, K., Dao, M., Suresh, S., Palazoglu, A. & Ortiz, C. Nanoscale heterogeneity promotes energy dissipation in bone. Nat. Mater. 6, 454\u2013462 (2007).","journal-title":"Nat. Mater."},{"key":"477_CR21","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.bone.2004.02.024","volume":"35","author":"T Hassenkam","year":"2004","unstructured":"Hassenkam, T. et al. High-resolution AFM imaging of intact and fractured trabecular bone. Bone 35, 4\u201310 (2004).","journal-title":"Bone"},{"key":"477_CR22","unstructured":"Thurner, P. J. et al. in Modern Research and Educational Topics in Microscopy (eds M\u00e9ndez-Vilas, A. D. & D\u00edaz, J.) 37\u201348 (Formatex, 2007)."},{"key":"477_CR23","doi-asserted-by":"publisher","first-page":"105007","DOI":"10.1088\/1361-6501\/aa7e8a","volume":"28","author":"B Pan","year":"2017","unstructured":"Pan, B. & Wang, B. A flexible and accurate digital volume correlation method applicable to high-resolution volumetric images. Meas. Sci. Technol. 28, 105007 (2017).","journal-title":"Meas. Sci. Technol."},{"key":"477_CR24","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.piutam.2012.05.013","volume":"4","author":"AI Hussein","year":"2012","unstructured":"Hussein, A. I., Barbone, P. E. & Morgan, E. F. Digital volume correlation for study of the mechanics of whole bones. Procedia IUTAM 4, 116\u2013125 (2012).","journal-title":"Procedia IUTAM"},{"key":"477_CR25","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/BF02323555","volume":"39","author":"BK Bay","year":"1999","unstructured":"Bay, B. K., Smith, T. S., Fyhrie, D. P. & Saad, M. Digital volume correlation: three-dimensional strain mapping using X-ray tomography. Exp. Mech. 39, 217\u2013226 (1999).","journal-title":"Exp. Mech."},{"key":"477_CR26","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.jbiomech.2014.01.001","volume":"47","author":"BC Roberts","year":"2014","unstructured":"Roberts, B. C., Perilli, E. & Reynolds, K. J. Application of the digital volume correlation technique for the measurement of displacement and strain fields in bone: a literature review. J. Biomech. 47, 923\u2013934 (2014).","journal-title":"J. Biomech."},{"key":"477_CR27","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1016\/j.bone.2010.02.025","volume":"46","author":"HD Barth","year":"2010","unstructured":"Barth, H. D., Launey, M. E., MacDowell, A. A., Ager, J. W. III & Ritchie, R. O. On the effect of X-ray irradiation on the deformation and fracture behavior of human cortical bone. Bone 46, 1475\u20131485 (2010).","journal-title":"Bone"},{"key":"477_CR28","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1002\/jor.1100150116","volume":"15","author":"JD Currey","year":"1997","unstructured":"Currey, J. D. et al. Effects of ionizing radiation on the mechanical properties of human bone. J. Orthop. Res. 15, 111\u2013117 (1997).","journal-title":"J. Orthop. Res."},{"key":"477_CR29","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.joca.2016.12.014","volume":"25","author":"KA Staines","year":"2017","unstructured":"Staines, K. A., Poulet, B., Wentworth, D. N. & Pitsillides, A. A. The STR\/ort mouse model of spontaneous osteoarthritis\u2013an update. Osteoarthr. Cartilage 25, 802\u2013808 (2017).","journal-title":"Osteoarthr. Cartilage"},{"key":"477_CR30","doi-asserted-by":"publisher","first-page":"192014","DOI":"10.1088\/1742-6596\/425\/19\/192014","volume":"425","author":"A De Fanis","year":"2013","unstructured":"De Fanis, A., Pe\u0161i\u0107, Z., Wagner, U. & Rau, C. Fast X-ray imaging at beamline I13L at Diamond Light Source. J. Phys. Conf. Ser. 425, 192014 (2013).","journal-title":"J. Phys. Conf. Ser."},{"key":"477_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9300","volume":"6","author":"S Karagadde","year":"2015","unstructured":"Karagadde, S. et al. Transgranular liquation cracking of grains in the semi-solid state. Nat. Commun. 6, 8300 (2015).","journal-title":"Nat. Commun."},{"key":"477_CR32","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5464","volume":"5","author":"K Kareh","year":"2014","unstructured":"Kareh, K., Lee, P., Atwood, R., Connolley, T. & Gourlay, C. Revealing the micromechanisms behind semi-solid metal deformation with time-resolved X-ray tomography. Nat. Commun. 5, 4464 (2014).","journal-title":"Nat. Commun."},{"key":"477_CR33","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1243\/03093247JSA436","volume":"43","author":"BK Bay","year":"2008","unstructured":"Bay, B. K. Methods and applications of digital volume correlation. J. Strain Anal. Eng. Des. 43, 745\u2013760 (2008).","journal-title":"J. Strain Anal. Eng. Des."},{"key":"477_CR34","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1111\/j.1749-6632.2009.05240.x","volume":"1192","author":"MB Goldring","year":"2010","unstructured":"Goldring, M. B. & Goldring, S. R. Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis. Ann. N. Y. Acad. Sci. 1192, 230\u2013237 (2010).","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"477_CR35","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nrrheum.2010.197","volume":"7","author":"RJ Lories","year":"2011","unstructured":"Lories, R. J. & Luyten, F. P. The bone\u2013cartilage unit in osteoarthritis. Nat. Rev. Rheumatol. 7, 43\u201349 (2011).","journal-title":"Nat. Rev. Rheumatol."},{"key":"477_CR36","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nrrheum.2009.107","volume":"5","author":"R M\u00fcller","year":"2009","unstructured":"M\u00fcller, R. Hierarchical microimaging of bone structure and function. Nat. Rev. Rheumatol. 5, 373\u2013381 (2009).","journal-title":"Nat. Rev. Rheumatol."},{"key":"477_CR37","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/j.jbiomech.2011.01.038","volume":"44","author":"S Yamada","year":"2011","unstructured":"Yamada, S., Tadano, S. & Fujisaki, K. Residual stress distribution in rabbit limb bones. J. Biomech. 44, 1285\u20131290 (2011).","journal-title":"J. Biomech."},{"key":"477_CR38","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.1021\/nl051584b","volume":"5","author":"HS Gupta","year":"2005","unstructured":"Gupta, H. S. et al. Nanoscale deformation mechanisms in bone. Nano Lett. 5, 2108\u20132111 (2005).","journal-title":"Nano Lett."},{"key":"477_CR39","doi-asserted-by":"publisher","first-page":"4389","DOI":"10.1016\/j.actbio.2012.07.042","volume":"8","author":"SE Campbell","year":"2012","unstructured":"Campbell, S. E., Ferguson, V. L. & Hurley, D. C. Nanomechanical mapping of the osteochondral interface with contact resonance force microscopy and nanoindentation. Acta Biomaterialia 8, 4389\u20134396 (2012).","journal-title":"Acta Biomaterialia"},{"key":"477_CR40","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/jor.1100120506","volume":"12","author":"P Mente","year":"1994","unstructured":"Mente, P. & Lewis, J. L. Elastic modulus of calcified cartilage is an order of magnitude less than that of subchondral bone. J. Orthop. Res. 12, 637\u2013647 (1994).","journal-title":"J. Orthop. Res."},{"key":"477_CR41","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1016\/j.joca.2015.05.012","volume":"23","author":"E Hargrave-Thomas","year":"2015","unstructured":"Hargrave-Thomas, E., van Sloun, F., Dickinson, M., Broom, N. & Thambyah, A. Multi-scalar mechanical testing of the calcified cartilage and subchondral bone comparing healthy vs early degenerative states. Osteoarthr. Cartilage 23, 1755\u20131762 (2015).","journal-title":"Osteoarthr. Cartilage"},{"key":"477_CR42","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1016\/j.joca.2007.04.003","volume":"15","author":"M Doube","year":"2007","unstructured":"Doube, M., Firth, E. & Boyde, A. Variations in articular calcified cartilage by site and exercise in the 18-month-old equine distal metacarpal condyle. Osteoarthr. Cartilage 15, 1283\u20131292 (2007).","journal-title":"Osteoarthr. Cartilage"},{"key":"477_CR43","first-page":"359","volume":"41","author":"J Day","year":"2004","unstructured":"Day, J. et al. Adaptation of subchondral bone in osteoarthritis. Biorheology 41, 359\u2013368 (2004).","journal-title":"Biorheology"},{"key":"477_CR44","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1136\/ard.56.4.247","volume":"56","author":"B Li","year":"1997","unstructured":"Li, B. & Aspden, R. M. Mechanical and material properties of the subchondral bone plate from the femoral head of patients with osteoarthritis or osteoporosis. Ann. Rheum. Dis. 56, 247\u2013254 (1997).","journal-title":"Ann. Rheum. Dis."},{"key":"477_CR45","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1359\/jbmr.1997.12.4.641","volume":"12","author":"B Li","year":"1997","unstructured":"Li, B. & Aspden, R. M. Composition and mechanical properties of cancellous bone from the femoral head of patients with osteoporosis or osteoarthritis. J. Bone Miner. Res. 12, 641\u2013651 (1997).","journal-title":"J. Bone Miner. Res."},{"key":"477_CR46","doi-asserted-by":"publisher","first-page":"406","DOI":"10.7150\/ijbs.4221","volume":"8","author":"A Jaiprakash","year":"2012","unstructured":"Jaiprakash, A. et al. Phenotypic characterization of osteoarthritic osteocytes from the sclerotic zones: a possible pathological role in subchondral bone sclerosis. Int. J. Biol. Sci. 8, 406\u2013417 (2012).","journal-title":"Int. J. Biol. Sci."},{"key":"477_CR47","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.1002\/art.24489","volume":"60","author":"D Couchourel","year":"2009","unstructured":"Couchourel, D. et al. Altered mineralization of human osteoarthritic osteoblasts is attributable to abnormal type I collagen production. Arthritis Rheum. 60, 1438\u20131450 (2009).","journal-title":"Arthritis Rheum."},{"key":"477_CR48","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/j.joca.2015.01.012","volume":"23","author":"B Poulet","year":"2015","unstructured":"Poulet, B. et al. Intermittent applied mechanical loading induces subchondral bone thickening that may be intensified locally by contiguous articular cartilage lesions. Osteoarthr. Cartilage 23, 940\u2013948 (2015).","journal-title":"Osteoarthr. Cartilage"},{"key":"477_CR49","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/j.jbiomech.2006.06.004","volume":"40","author":"L Van Ruijven","year":"2007","unstructured":"Van Ruijven, L., Mulder, L. & Van Eijden, T. Variations in mineralization affect the stress and strain distributions in cortical and trabecular bone. J. Biomech. 40, 1211\u20131218 (2007).","journal-title":"J. Biomech."},{"key":"477_CR50","first-page":"196","volume":"117","author":"S Mori","year":"1993","unstructured":"Mori, S., Harruff, R. & Burr, D. Microcracks in articular calcified cartilage of human femoral heads. Arch. Pathol. Lab. Med. 117, 196\u2013198 (1993).","journal-title":"Arch. Pathol. Lab. Med."},{"key":"477_CR51","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.bone.2011.11.030","volume":"51","author":"J Pan","year":"2012","unstructured":"Pan, J. et al. Elevated cross-talk between subchondral bone and cartilage in osteoarthritic joints. Bone 51, 212\u2013217 (2012).","journal-title":"Bone"},{"key":"477_CR52","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.bone.2011.10.010","volume":"51","author":"S Suri","year":"2012","unstructured":"Suri, S. & Walsh, D. A. Osteochondral alterations in osteoarthritis. Bone 51, 204\u2013211 (2012).","journal-title":"Bone"},{"key":"477_CR53","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.jbiomech.2016.12.025","volume":"52","author":"B Pouran","year":"2017","unstructured":"Pouran, B. et al. Solute transport at the interface of cartilage and subchondral bone plate: effect of micro-architecture. J. Biomech. 52, 148\u2013154 (2017).","journal-title":"J. Biomech."},{"key":"477_CR54","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.bone.2005.08.020","volume":"38","author":"P Muir","year":"2006","unstructured":"Muir, P. et al. Role of endochondral ossification of articular cartilage and functional adaptation of the subchondral plate in the development of fatigue microcracking of joints. Bone 38, 342\u2013349 (2006).","journal-title":"Bone"},{"key":"477_CR55","doi-asserted-by":"publisher","first-page":"9600","DOI":"10.3390\/ijms16059600","volume":"16","author":"S Laverty","year":"2015","unstructured":"Laverty, S., Lacourt, M., Gao, C., Henderson, J. & Boyde, A. High density infill in cracks and protrusions from the articular calcified cartilage in osteoarthritis in standardbred horse carpal bones. Int. J. Mol. Sci. 16, 9600\u20139611 (2015).","journal-title":"Int. J. Mol. Sci."},{"key":"477_CR56","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1111\/joa.12226","volume":"225","author":"A Boyde","year":"2014","unstructured":"Boyde, A. et al. On fragmenting, densely mineralised acellular protrusions into articular cartilage and their possible role in osteoarthritis. J. Anat. 225, 436\u2013446 (2014).","journal-title":"J. Anat."},{"key":"477_CR57","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1111\/joa.12177","volume":"224","author":"SM Turley","year":"2014","unstructured":"Turley, S. M., Thambyah, A., Riggs, C. M., Firth, E. C. & Broom, N. D. Microstructural changes in cartilage and bone related to repetitive overloading in an equine athlete model. J. Anat. 224, 647\u2013658 (2014).","journal-title":"J. Anat."},{"key":"477_CR58","doi-asserted-by":"publisher","first-page":"470","DOI":"10.22203\/eCM.v021a35","volume":"21","author":"A Boyde","year":"2011","unstructured":"Boyde, A. et al. Cartilage damage involving extrusion of mineralisable matrix from the articular calcified cartilage and subchondral bone. Eur. Cells Mater. 21, 470\u2013478 (2011).","journal-title":"Eur. Cells Mater."},{"key":"477_CR59","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1046\/j.1469-7580.2003.00213.x","volume":"203","author":"A Boyde","year":"2003","unstructured":"Boyde, A. The real response of bone to exercise. J. Anat. 203, 173\u2013189 (2003).","journal-title":"J. Anat."},{"key":"477_CR60","doi-asserted-by":"publisher","first-page":"330","DOI":"10.2460\/ajvr.69.3.330","volume":"69","author":"FH Comhaire","year":"2008","unstructured":"Comhaire, F. H. & Snaps, F. Comparison of two canine registry databases on the prevalence of hip dysplasia by breed and the relationship of dysplasia with body weight and height. Am. J. Vet. Res. 69, 330\u2013333 (2008).","journal-title":"Am. J. Vet. Res."},{"key":"477_CR61","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1530\/JOE-13-0276","volume":"219","author":"K Staines","year":"2013","unstructured":"Staines, K., Pollard, A., McGonnell, I., Farquharson, C. & Pitsillides, A. Cartilage to bone transitions in health and disease. J. Endocrinol. 219, R1\u2013R12 (2013).","journal-title":"J. Endocrinol."},{"key":"477_CR62","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1002\/art.39508","volume":"68","author":"K Staines","year":"2016","unstructured":"Staines, K. et al. Endochondral growth defect and deployment of transient chondrocyte behaviors underlie osteoarthritis onset in a natural murine model. Arthritis Rheumatol. 68, 880\u2013891 (2016).","journal-title":"Arthritis Rheumatol."},{"key":"477_CR63","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/nrrheum.2011.129","volume":"7","author":"AA Pitsillides","year":"2011","unstructured":"Pitsillides, A. A. & Beier, F. Cartilage biology in osteoarthritis\u2014lessons from developmental biology. Nat. Rev. Rheumatology 7, 654\u2013663 (2011).","journal-title":"Nat. Rev. Rheumatology"},{"key":"477_CR64","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1007\/s11837-011-0217-9","volume":"64","author":"C Puncreobutr","year":"2012","unstructured":"Puncreobutr, C., Lee, P., Hamilton, R. & Phillion, A. Quantitative 3D characterization of solidification structure and defect evolution in Al alloys. JOM 64, 89\u201395 (2012).","journal-title":"JOM"},{"key":"477_CR65","doi-asserted-by":"publisher","first-page":"43","DOI":"10.3389\/fmats.2017.00043","volume":"4","author":"J Maksimcuka","year":"2017","unstructured":"Maksimcuka, J. et al. X-ray tomographic imaging of tensile deformation modes of electrospun biodegradable polyester fibers. Front. Mater. 4, 43 (2017).","journal-title":"Front. Mater."},{"key":"477_CR66","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1002\/art.27765","volume":"63","author":"B Poulet","year":"2011","unstructured":"Poulet, B., Hamilton, R. W., Shefelbine, S. & Pitsillides, A. A. Characterizing a novel and adjustable noninvasive murine joint loading model. Arthritis Rheum. 63, 137\u2013147 (2011).","journal-title":"Arthritis Rheum."},{"key":"477_CR67","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1016\/j.bone.2006.06.013","volume":"39","author":"A Nazarian","year":"2006","unstructured":"Nazarian, A., Stauber, M., Zurakowski, D., Snyder, B. D. & M\u00fcller, R. The interaction of microstructure and volume fraction in predicting failure in cancellous bone. Bone 39, 1196\u20131202 (2006).","journal-title":"Bone"},{"key":"477_CR68","doi-asserted-by":"publisher","first-page":"2522","DOI":"10.1002\/pssa.201184272","volume":"208","author":"C Rau","year":"2011","unstructured":"Rau, C., Wagner, U., Pe\u0161i\u0107, Z. & De Fanis, A. Coherent imaging at the Diamond beamline I13. Physica Status Solidi A 208, 2522\u20132525 (2011).","journal-title":"Physica Status Solidi A"},{"key":"477_CR69","doi-asserted-by":"publisher","first-page":"182003","DOI":"10.1088\/1742-6596\/425\/18\/182003","volume":"425","author":"Z Pe\u0161i\u0107","year":"2013","unstructured":"Pe\u0161i\u0107, Z., De Fanis, A., Wagner, U. & Rau, C. Experimental stations at I13 beamline at Diamond Light Source. J. Phys. Conf. Ser. 425, 182003 (2013).","journal-title":"J. Phys. Conf. Ser."},{"key":"477_CR70","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.jmbbm.2011.12.009","volume":"8","author":"D Christen","year":"2012","unstructured":"Christen, D. et al. Deformable image registration and 3D strain mapping for the quantitative assessment of cortical bone microdamage. J. Mech. Behav. Biomed. Mater. 8, 184\u2013193 (2012).","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"477_CR71","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.bone.2009.04.248","volume":"45","author":"R Voide","year":"2009","unstructured":"Voide, R. et al. Time-lapsed assessment of microcrack initiation and propagation in murine cortical bone at submicrometer resolution. Bone 45, 164\u2013173 (2009).","journal-title":"Bone"},{"key":"477_CR72","doi-asserted-by":"publisher","first-page":"2229","DOI":"10.1118\/1.3697525","volume":"39","author":"A Pacureanu","year":"2012","unstructured":"Pacureanu, A., Langer, M., Boller, E., Tafforeau, P. & Peyrin, F. Nanoscale imaging of the bone cell network with synchrotron X\u2010ray tomography: optimization of acquisition setup. Med. Phys. 39, 2229\u20132238 (2012).","journal-title":"Med. Phys."},{"key":"477_CR73","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1107\/S1600577515002283","volume":"22","author":"M Basham","year":"2015","unstructured":"Basham, M. et al. Data analysis workbench (DAWN). J. Synchrotron Radiat. 22, 853\u2013858 (2015).","journal-title":"J. Synchrotron Radiat."},{"key":"477_CR74","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1107\/S160057751601479X","volume":"23","author":"V Titarenko","year":"2016","unstructured":"Titarenko, V. Analytical formula for two-dimensional ring artefact suppression. J. Synchrotron Radiat. 23, 1447\u20131461 (2016).","journal-title":"J. Synchrotron Radiat."},{"key":"477_CR75","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1016\/j.medengphy.2013.02.001","volume":"35","author":"K Madi","year":"2013","unstructured":"Madi, K. et al. Computation of full-field displacements in a scaffold implant using digital volume correlation and finite element analysis. Med. Eng. Phys. 35, 1298\u20131312 (2013).","journal-title":"Med. Eng. Phys."},{"key":"477_CR76","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1016\/j.media.2008.03.008","volume":"12","author":"KZ Abd-Elmoniem","year":"2008","unstructured":"Abd-Elmoniem, K. Z., Stuber, M. & Prince, J. L. Direct three-dimensional myocardial strain tensor quantification and tracking using zHARP. Med. Image Anal. 12, 778\u2013786 (2008).","journal-title":"Med. Image Anal."},{"key":"477_CR77","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.bone.2005.07.022","volume":"37","author":"RL De Souza","year":"2005","unstructured":"De Souza, R. L. et al. Non-invasive axial loading of mouse tibiae increases cortical bone formation and modifies trabecular organization: a new model to study cortical and cancellous compartments in a single loaded element. Bone 37, 810\u2013818 (2005).","journal-title":"Bone"}],"container-title":["Nature Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41551-019-0477-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-019-0477-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-019-0477-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T22:40:47Z","timestamp":1671230447000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41551-019-0477-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,25]]},"references-count":77,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["477"],"URL":"https:\/\/doi.org\/10.1038\/s41551-019-0477-1","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.736989891.793572433","asserted-by":"object"}]},"ISSN":["2157-846X"],"issn-type":[{"value":"2157-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,25]]},"assertion":[{"value":"12 March 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}