{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T07:11:27Z","timestamp":1793949087909,"version":"4.8.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Matrix metalloproteinases (MMPs) play a crucial role in enzymatically digesting cartilage extracellular matrix (ECM) components, resulting in degraded cartilage with altered mechanical loading capacity. Overexpression of MMPs is often caused by trauma, physiologic conditions and by disease. To understand the synergistic impact MMPs have on cartilage biomechanical properties, MMPs from two subfamilies: collagenase (MMP-1) and gelatinase (MMP-9) were investigated in this study. Three different ratios of MMP-1 (c) and MMP-9 (g), c1:g1, c3:g1 and c1:g3 were considered to develop a degradation model. Thirty samples, harvested from bovine femoral condyles, were treated in groups of 10 with one concentration of enzyme mixture. Each sample was tested in a healthy state prior to introducing degradative enzymes to establish a baseline. Samples were subjected to indentation loading up to 20% bulk strain. Both control and treated samples were mechanically and histologically assessed to determine the impact of degradation. Young\u2019s modulus and peak load of the tissue under indentation were compared between the control and degraded cartilage explants. Cartilage degraded with the c3:g1 enzyme concentration resulted in maximum 33% reduction in stiffness and peak load compared to the\u00a0other two concentrations. The abundance of collagenase is more responsible for cartilage degradation and reduced mechanical integrity.<\/jats:p>","DOI":"10.1038\/s41598-021-93744-1","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T06:24:02Z","timestamp":1626157442000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["An in vitro investigation to understand the synergistic role of MMPs-1 and 9 on articular cartilage biomechanical properties"],"prefix":"10.1038","volume":"11","author":[{"given":"Allison","family":"Mixon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Savage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Suparno","family":"Bahar-Moni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malek","family":"Adouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvir","family":"Faisal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"93744_CR1","first-page":"869","volume":"62","author":"KE Barbour","year":"2013","unstructured":"Barbour, K. E. et al. Prevalence of doctor-diagnosed arthritis and arthritis-attributable activity limitation\u2014United States, 2010\u20132012. MMWR Morb. Mortal. Wkly Rep. 62, 869 (2013).","journal-title":"MMWR Morb. Mortal. Wkly Rep."},{"key":"93744_CR2","doi-asserted-by":"publisher","first-page":"e000279","DOI":"10.1136\/rmdopen-2016-000279","volume":"2","author":"L Punzi","year":"2016","unstructured":"Punzi, L. et al. Post-traumatic arthritis: Overview on pathogenic mechanisms and role of inflammation. RMD Open 2, e000279\u2013e000279. https:\/\/doi.org\/10.1136\/rmdopen-2016-000279 (2016).","journal-title":"RMD Open"},{"key":"93744_CR3","doi-asserted-by":"publisher","first-page":"529","DOI":"10.2741\/1817","volume":"11","author":"PS Burrage","year":"2006","unstructured":"Burrage, P. S., Mix, K. S. & Brinckerhoff, C. E. Matrix metalloproteinases: Role in arthritis. Front. Biosci. 11, 529\u2013543 (2006).","journal-title":"Front. Biosci."},{"key":"93744_CR4","doi-asserted-by":"publisher","first-page":"95","DOI":"10.2106\/00004623-198466010-00013","volume":"66","author":"R Brocklehurst","year":"1984","unstructured":"Brocklehurst, R. et al. The composition of normal and osteoarthritic articular cartilage from human knee joints. With special reference to unicompartmental replacement and osteotomy of the knee. JBJS 66, 95\u2013106 (1984).","journal-title":"JBJS"},{"key":"93744_CR5","doi-asserted-by":"publisher","first-page":"2859","DOI":"10.1172\/JCI118357","volume":"96","author":"AP Hollander","year":"1995","unstructured":"Hollander, A. P. et al. Damage to type II collagen in aging and osteoarthritis starts at the articular surface, originates around chondrocytes, and extends into the cartilage with progressive degeneration. J. Clin. Investig. 96, 2859\u20132869 (1995).","journal-title":"J. Clin. Investig."},{"key":"93744_CR6","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/0304-4165(73)90093-7","volume":"297","author":"G Kempson","year":"1973","unstructured":"Kempson, G., Muir, H., Pollard, C. & Tuke, M. The tensile properties of the cartilage of human femoral condyles related to the content of collagen and glycosaminoglycans. Biochim. Biophys. Acta 297, 456\u2013472 (1973).","journal-title":"Biochim. Biophys. Acta"},{"key":"93744_CR7","unstructured":"Pool, A. R. in Arthritis and Allied Conditions: A Textbook of Rheumatology Vol. 1 (ed William J Koopman) 226\u2013284 (Lippincott, Williams and Wilkins, 2001)."},{"key":"93744_CR8","unstructured":"Kempson, G. E. in Adult Articular Cartilage (ed Michael Alexander Reykers Freeman) Ch. 313\u2013414, (Pitman Medical, 1979)."},{"key":"93744_CR9","doi-asserted-by":"publisher","first-page":"954","DOI":"10.2106\/00004623-197254050-00002","volume":"54","author":"C Weiss","year":"1972","unstructured":"Weiss, C. & Mirow, S. An ultrastructural study of osteoarthritic changes in the articular cartilage of human knees. JBJS 54, 954\u2013972 (1972).","journal-title":"JBJS"},{"key":"93744_CR10","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1136\/ard.57.4.237","volume":"57","author":"HE Panula","year":"1998","unstructured":"Panula, H. E. et al. Articular cartilage superficial zone collagen birefringence reduced and cartilage thickness increased before surface fibrillation in experimental osteoarthritis. Ann. Rheum. Dis. 57, 237\u2013245 (1998).","journal-title":"Ann. Rheum. Dis."},{"key":"93744_CR11","first-page":"487","volume":"47","author":"JA Buckwalter","year":"1998","unstructured":"Buckwalter, J. A. & Mankin, H. J. Articular cartilage: Degeneration and osteoarthritis, repair, regeneration, and transplantation. Instr. Course Lect. 47, 487\u2013504 (1998).","journal-title":"Instr. Course Lect."},{"key":"93744_CR12","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1172\/JCI119316","volume":"99","author":"RC Billinghurst","year":"1997","unstructured":"Billinghurst, R. C. et al. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J. Clin. Investig. 99, 1534\u20131545 (1997).","journal-title":"J. Clin. Investig."},{"key":"93744_CR13","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3109\/03008207.2015.1099636","volume":"57","author":"A N\u00e4kki","year":"2016","unstructured":"N\u00e4kki, A. et al. Association study of MMP8 gene in osteoarthritis. Connect. Tissue Res. 57, 44\u201352 (2016).","journal-title":"Connect. Tissue Res."},{"key":"93744_CR14","doi-asserted-by":"publisher","first-page":"116786","DOI":"10.1016\/j.lfs.2019.116786","volume":"234","author":"E-SE Mehana","year":"2019","unstructured":"Mehana, E.-S.E., Khafaga, A. F. & El-Blehi, S. S. The role of matrix metalloproteinases in osteoarthritis pathogenesis: An updated review. Life Sci. 234, 116786 (2019).","journal-title":"Life Sci."},{"key":"93744_CR15","doi-asserted-by":"publisher","first-page":"14811","DOI":"10.4238\/2015.November.18.46","volume":"14","author":"G Zeng","year":"2015","unstructured":"Zeng, G., Chen, A., Li, W., Song, J. & Gao, C. High MMP-1, MMP-2, and MMP-9 protein levels in osteoarthritis. Genet. Mol. Res. 14, 14811\u201314822 (2015).","journal-title":"Genet. Mol. Res."},{"key":"93744_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-016-0009-6","volume":"8","author":"Y-O Son","year":"2017","unstructured":"Son, Y.-O. et al. Estrogen-related receptor \u03b3 causes osteoarthritis by upregulating extracellular matrix-degrading enzymes. Nat. Commun. 8, 1\u201311 (2017).","journal-title":"Nat. Commun."},{"key":"93744_CR17","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.cub.2012.04.012","volume":"22","author":"SK Sarkar","year":"2012","unstructured":"Sarkar, S. K., Marmer, B., Goldberg, G. & Neuman, K. C. Single-molecule tracking of collagenase on native type I collagen fibrils reveals degradation mechanism. Curr. Biol. 22, 1047\u20131056 (2012).","journal-title":"Curr. Biol."},{"key":"93744_CR18","doi-asserted-by":"publisher","first-page":"e11043","DOI":"10.1371\/journal.pone.0011043","volume":"5","author":"G Rosenblum","year":"2010","unstructured":"Rosenblum, G. et al. Direct visualization of protease action on collagen triple helical structure. PLoS ONE 5, e11043 (2010).","journal-title":"PLoS ONE"},{"key":"93744_CR19","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1007\/s10237-019-01178-6","volume":"18","author":"B Powell","year":"2019","unstructured":"Powell, B., Malaspina, D. C., Szleifer, I. & Dhaher, Y. Effect of collagenase\u2013gelatinase ratio on the mechanical properties of a collagen fibril: A combined Monte Carlo\u2013molecular dynamics study. Biomech. Model. Mechanobiol. 18, 1809\u20131819. https:\/\/doi.org\/10.1007\/s10237-019-01178-6 (2019).","journal-title":"Biomech. Model. Mechanobiol."},{"key":"93744_CR20","doi-asserted-by":"publisher","first-page":"e24029","DOI":"10.1371\/journal.pone.0024029","volume":"6","author":"IE Collier","year":"2011","unstructured":"Collier, I. E. et al. Diffusion of MMPs on the surface of collagen fibrils: the mobile cell surface\u2013collagen substratum interface. PLoS ONE 6, e24029 (2011).","journal-title":"PLoS ONE"},{"key":"93744_CR21","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/S0014-5793(01)02204-9","volume":"491","author":"SJ Atkinson","year":"2001","unstructured":"Atkinson, S. J., Patterson, M. L., Butler, M. J. & Murphy, G. Membrane type 1 matrix metalloproteinase and gelatinase A synergistically degrade type 1 collagen in a cell model. FEBS Lett. 491, 222\u2013226 (2001).","journal-title":"FEBS Lett."},{"key":"93744_CR22","doi-asserted-by":"publisher","first-page":"17124","DOI":"10.1074\/jbc.271.29.17124","volume":"271","author":"V Kn\u00e4uper","year":"1996","unstructured":"Kn\u00e4uper, V. et al. Cellular mechanisms for human procollagenase-3 (MMP-13) activation: Evidence that MT1-MMP (MMP-14) and gelatinase A (MMP-2) are able to generate active enzyme. J. Biol. Chem. 271, 17124\u201317131 (1996).","journal-title":"J. Biol. Chem."},{"key":"93744_CR23","doi-asserted-by":"publisher","first-page":"4895050","DOI":"10.1155\/2016\/4895050","volume":"2016","author":"BJ Rose","year":"2016","unstructured":"Rose, B. J. & Kooyman, D. L. A tale of two joints: The role of matrix metalloproteases in cartilage biology. Dis. Mark. 2016, 4895050. https:\/\/doi.org\/10.1155\/2016\/4895050 (2016).","journal-title":"Dis. Mark."},{"key":"93744_CR24","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1111\/j.1440-1827.2010.02547.x","volume":"60","author":"T Shiomi","year":"2010","unstructured":"Shiomi, T., Lema\u00eetre, V., D\u2019Armiento, J. & Okada, Y. Matrix metalloproteinases, a disintegrin and metalloproteinases, and a disintegrin and metalloproteinases with thrombospondin motifs in non-neoplastic diseases. Pathol. Int. 60, 477\u2013496 (2010).","journal-title":"Pathol. Int."},{"key":"93744_CR25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/ar792","volume":"5","author":"S Elliott","year":"2003","unstructured":"Elliott, S., Hays, E., Mayor, M., Sporn, M. & Vincenti, M. The triterpenoid CDDO inhibits expression of matrix metalloproteinase-1, matrix metalloproteinase-13 and Bcl-3 in primary human chondrocytes. Arthritis Res. Ther. 5, 1\u20137 (2003).","journal-title":"Arthritis Res. Ther."},{"key":"93744_CR26","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.3390\/cells9051076","volume":"9","author":"H Laronha","year":"2020","unstructured":"Laronha, H. & Caldeira, J. Structure and function of human matrix metalloproteinases. Cells 9, 1076 (2020).","journal-title":"Cells"},{"key":"93744_CR27","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.joca.2012.11.008","volume":"21","author":"D Kumar","year":"2013","unstructured":"Kumar, D., Manal, K. T. & Rudolph, K. S. Knee joint loading during gait in healthy controls and individuals with knee osteoarthritis. Osteoarthritis Cartilage 21, 298\u2013305 (2013).","journal-title":"Osteoarthritis Cartilage"},{"key":"93744_CR28","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.jbiomech.2015.12.016","volume":"49","author":"H Marouane","year":"2016","unstructured":"Marouane, H., Shirazi-Adl, A. & Adouni, M. Alterations in knee contact forces and centers in stance phase of gait: A detailed lower extremity musculoskeletal model. J. Biomech. 49, 185\u2013192 (2016).","journal-title":"J. Biomech."},{"key":"93744_CR29","doi-asserted-by":"publisher","first-page":"e0187583","DOI":"10.1371\/journal.pone.0187583","volume":"12","author":"S Meireles","year":"2017","unstructured":"Meireles, S. et al. Medial knee loading is altered in subjects with early osteoarthritis during gait but not during step-up-and-over task. PLoS ONE 12, e0187583 (2017).","journal-title":"PLoS ONE"},{"key":"93744_CR30","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.gaitpost.2016.01.016","volume":"45","author":"S Meireles","year":"2016","unstructured":"Meireles, S. et al. Knee contact forces are not altered in early knee osteoarthritis. Gait Posture 45, 115\u2013120 (2016).","journal-title":"Gait Posture"},{"key":"93744_CR31","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/j.jbiomech.2005.02.018","volume":"39","author":"WC Bae","year":"2006","unstructured":"Bae, W. C., Lewis, C. W., Levenston, M. E. & Sah, R. L. Indentation testing of human articular cartilage: Effects of probe tip geometry and indentation depth on intra-tissue strain. J. Biomech. 39, 1039\u20131047. https:\/\/doi.org\/10.1016\/j.jbiomech.2005.02.018 (2006).","journal-title":"J. Biomech."},{"key":"93744_CR32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.joca.2006.06.007","volume":"15","author":"WC Bae","year":"2007","unstructured":"Bae, W. C., Schumacher, B. L. & Sah, R. L. Indentation probing of human articular cartilage: Effect on chondrocyte viability. Osteoarthr. Cartil. 15, 9\u201318. https:\/\/doi.org\/10.1016\/j.joca.2006.06.007 (2007).","journal-title":"Osteoarthr. Cartil."},{"key":"93744_CR33","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.1088\/0031-9155\/44\/11\/303","volume":"44","author":"J T\u00f6yr\u00e4s","year":"1999","unstructured":"T\u00f6yr\u00e4s, J., Rieppo, J., Nieminen, M., Helminen, H. & Jurvelin, J. Characterization of enzymatically induced degradation of articular cartilage using high frequency ultrasound. Phys. Med. Biol. 44, 2723 (1999).","journal-title":"Phys. Med. Biol."},{"key":"93744_CR34","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/j.jbiomech.2013.11.050","volume":"47","author":"S Grenier","year":"2014","unstructured":"Grenier, S., Bhargava, M. M. & Torzilli, P. A. An in vitro model for the pathological degradation of articular cartilage in osteoarthritis. J. Biomech. 47, 645\u2013652 (2014).","journal-title":"J. Biomech."},{"key":"93744_CR35","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1002\/jor.1100080307","volume":"8","author":"MB Schmidt","year":"1990","unstructured":"Schmidt, M. B., Mow, V. C., Chun, L. E. & Eyre, D. R. Effects of proteoglycan extraction on the tensile behavior of articular cartilage. J. Orthop. Res. 8, 353\u2013363 (1990).","journal-title":"J. Orthop. Res."},{"key":"93744_CR36","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.ultrasmedbio.2004.03.005","volume":"30","author":"S Saarakkala","year":"2004","unstructured":"Saarakkala, S. et al. Ultrasonic quantitation of superficial degradation of articular cartilage. Ultrasound Med. Biol. 30, 783\u2013792 (2004).","journal-title":"Ultrasound Med. Biol."},{"key":"93744_CR37","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/j.ultrasmedbio.2007.12.006","volume":"34","author":"Q Wang","year":"2008","unstructured":"Wang, Q. et al. Real-time ultrasonic assessment of progressive proteoglycan depletion in articular cartilage. Ultrasound Med. Biol. 34, 1085\u20131092 (2008).","journal-title":"Ultrasound Med. Biol."},{"key":"93744_CR38","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1002\/(SICI)1097-4636(1999)48:4<482::AID-JBM13>3.0.CO;2-M","volume":"48","author":"T Lyyra","year":"1999","unstructured":"Lyyra, T., Kiviranta, I., V\u00e4\u00e4t\u00e4inen, U., Helminen, H. J. & Jurvelin, J. S. In vivo characterization of indentation stiffness of articular cartilage in the normal human knee. J. Biomed. Mater. Res. 48, 482\u2013487 (1999).","journal-title":"J. Biomed. Mater. Res."},{"key":"93744_CR39","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/S0021-9290(02)00052-0","volume":"35","author":"R Korhonen","year":"2002","unstructured":"Korhonen, R. et al. Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression and indentation. J. Biomech. 35, 903\u2013909 (2002).","journal-title":"J. Biomech."},{"key":"93744_CR40","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1385\/1-59259-821-8:157","volume":"101","author":"AC Chen","year":"2004","unstructured":"Chen, A. C. et al. Mechanical characterization of native and tissue-engineered cartilage. Methods Mol. Med. 101, 157\u2013190. https:\/\/doi.org\/10.1385\/1-59259-821-8:157 (2004).","journal-title":"Methods Mol. Med."},{"key":"93744_CR41","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1016\/j.biocel.2007.12.006","volume":"40","author":"IM Clark","year":"2008","unstructured":"Clark, I. M., Swingler, T. E., Sampieri, C. L. & Edwards, D. R. The regulation of matrix metalloproteinases and their inhibitors. Int. J. Biochem. Cell Biol. 40, 1362\u20131378. https:\/\/doi.org\/10.1016\/j.biocel.2007.12.006 (2008).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"93744_CR42","first-page":"1585","volume":"25","author":"J Fernandes","year":"1998","unstructured":"Fernandes, J. et al. Collagenase-1 and collagenase-3 synthesis in normal and early experimental osteoarthritic canine cartilage: An immunohistochemical study. J. Rheumatol. 25, 1585\u20131594 (1998).","journal-title":"J. Rheumatol."},{"key":"93744_CR43","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1002\/art.1780400915","volume":"40","author":"F Moldovan","year":"1997","unstructured":"Moldovan, F., Pelletier, J. P., Hambor, J., Cloutier, J. M. & Martel-Pelletier, J. Collagenase-3 (matrix metalloprotease 13) is preferentially localized in the deep layer of human arthritic cartilage in situ. In vitro mimicking effect by transforming growth factor \u03b2. Arthritis Rheum. 40, 1653\u20131661 (1997).","journal-title":"Arthritis Rheum."},{"key":"93744_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1615\/critrevbiomedeng.v37.i1-2.10","volume":"37","author":"L Zhang","year":"2009","unstructured":"Zhang, L., Hu, J. & Athanasiou, K. A. The role of tissue engineering in articular cartilage repair and regeneration. Crit. Rev. Biomed. Eng. 37, 1\u201357. https:\/\/doi.org\/10.1615\/critrevbiomedeng.v37.i1-2.10 (2009).","journal-title":"Crit. Rev. Biomed. Eng."},{"key":"93744_CR45","doi-asserted-by":"publisher","first-page":"177","DOI":"10.3109\/14756366.2016.1161620","volume":"31","author":"A Jab\u0142o\u0144ska-Trypu\u0107","year":"2016","unstructured":"Jab\u0142o\u0144ska-Trypu\u0107, A., Matejczyk, M. & Rosochacki, S. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs. J. Enzyme Inhib. Med. Chem. 31, 177\u2013183. https:\/\/doi.org\/10.3109\/14756366.2016.1161620 (2016).","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"93744_CR46","doi-asserted-by":"publisher","first-page":"D704","DOI":"10.2741\/a388","volume":"4","author":"RL Smith","year":"1999","unstructured":"Smith, R. L. Degradative enzymes in osteoarthritis. Front. Biosci. 4, D704-712. https:\/\/doi.org\/10.2741\/a388 (1999).","journal-title":"Front. Biosci."},{"key":"93744_CR47","doi-asserted-by":"publisher","first-page":"3406","DOI":"10.1016\/j.jbiomech.2015.05.032","volume":"48","author":"G Peng","year":"2015","unstructured":"Peng, G., McNary, S. M., Athanasiou, K. A. & Reddi, A. H. The distribution of superficial zone protein (SZP)\/lubricin\/PRG4 and boundary mode frictional properties of the bovine diarthrodial joint. J. Biomech. 48, 3406\u20133412. https:\/\/doi.org\/10.1016\/j.jbiomech.2015.05.032 (2015).","journal-title":"J. Biomech."},{"key":"93744_CR48","unstructured":"Mookhtiar, K. & Van Wart, H. Clostridium histolyticum collagenases: a new look at some old enzymes. Matrix (Stuttgart, Germany). Supplement 1, 116\u2013126 (1992)."},{"key":"93744_CR49","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1002\/jor.1100120306","volume":"12","author":"K Athanasiou","year":"1994","unstructured":"Athanasiou, K., Agarwal, A. & Dzida, F. Comparative study of the intrinsic mechanical properties of the human acetabular and femoral head cartilage. J. Orthop. Res. 12, 340\u2013349 (1994).","journal-title":"J. Orthop. Res."},{"key":"93744_CR50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2474-11-231","volume":"11","author":"M Szarko","year":"2010","unstructured":"Szarko, M., Muldrew, K. & Bertram, J. E. Freeze-thaw treatment effects on the dynamic mechanical properties of articular cartilage. BMC Musculoskelet. Disord. 11, 1\u20138 (2010).","journal-title":"BMC Musculoskelet. Disord."},{"key":"93744_CR51","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1002\/term.2936","volume":"13","author":"T Ghassemi","year":"2019","unstructured":"Ghassemi, T. et al. A comparison study of different decellularization treatments on bovine articular cartilage. J. Tissue Eng. Regen. Med. 13, 1861\u20131871 (2019).","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"93744_CR52","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1136\/ard.2004.022434","volume":"64","author":"I Tchetverikov","year":"2005","unstructured":"Tchetverikov, I. et al. MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis. Ann. Rheum. Dis. 64, 694\u2013698. https:\/\/doi.org\/10.1136\/ard.2004.022434 (2005).","journal-title":"Ann. Rheum. Dis."},{"key":"93744_CR53","first-page":"133","volume":"40","author":"M Laasanen","year":"2003","unstructured":"Laasanen, M. et al. Biomechanical properties of knee articular cartilage. Biorheology 40, 133\u2013140 (2003).","journal-title":"Biorheology"},{"key":"93744_CR54","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1089\/ten.TEC.2019.0116","volume":"25","author":"JM Patel","year":"2019","unstructured":"Patel, J. M., Wise, B. C., Bonnevie, E. D. & Mauck, R. L. A systematic review and guide to mechanical testing for articular cartilage tissue engineering. Tissue Eng. Part C Methods 25, 593\u2013608. https:\/\/doi.org\/10.1089\/ten.TEC.2019.0116 (2019).","journal-title":"Tissue Eng. Part C Methods"},{"key":"93744_CR55","unstructured":"Chandwadkar, S. A. Indentation Protocol to Determine Viscoelastic Properties of Cartilage Before and After Crosslinking (2017)."},{"key":"93744_CR56","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1089\/ten.tea.2016.0191","volume":"23","author":"GR Meloni","year":"2017","unstructured":"Meloni, G. R., Fisher, M. B., Stoeckl, B. D., Dodge, G. R. & Mauck, R. L. Biphasic finite element modeling reconciles mechanical properties of tissue-engineered cartilage constructs across testing platforms. Tissue Eng. Part A 23, 663\u2013674. https:\/\/doi.org\/10.1089\/ten.tea.2016.0191 (2017).","journal-title":"Tissue Eng. Part A"},{"key":"93744_CR57","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1179\/his.1998.21.1.49","volume":"21","author":"G Callis","year":"1998","unstructured":"Callis, G. & Sterchi, D. Decalcification of bone: Literature review and practical study of various decalcifying agents methods, and their effects on bone histology. J. Histotechnol. 21, 49\u201358. https:\/\/doi.org\/10.1179\/his.1998.21.1.49 (1998).","journal-title":"J. Histotechnol."},{"key":"93744_CR58","doi-asserted-by":"publisher","first-page":"S113","DOI":"10.1016\/j.joca.2010.05.026","volume":"18","author":"N Schmitz","year":"2010","unstructured":"Schmitz, N., Laverty, S., Kraus, V. B. & Aigner, T. Basic methods in histopathology of joint tissues. Osteoarthr. Cartil. 18, S113\u2013S116. https:\/\/doi.org\/10.1016\/j.joca.2010.05.026 (2010).","journal-title":"Osteoarthr. Cartil."},{"key":"93744_CR59","doi-asserted-by":"publisher","first-page":"24","DOI":"10.2174\/1874312901206010024","volume":"6","author":"Y Sun","year":"2012","unstructured":"Sun, Y. et al. Histological examination of collagen and proteoglycan changes in osteoarthritic menisci. Open Rheumatol. J. 6, 24\u201332. https:\/\/doi.org\/10.2174\/1874312901206010024 (2012).","journal-title":"Open Rheumatol. J."},{"key":"93744_CR60","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1016\/s0021-9290(02)00052-0","volume":"35","author":"RK Korhonen","year":"2002","unstructured":"Korhonen, R. K. et al. Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression and indentation. J Biomech 35, 903\u2013909. https:\/\/doi.org\/10.1016\/s0021-9290(02)00052-0 (2002).","journal-title":"J Biomech"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-93744-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-93744-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-93744-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T06:16:48Z","timestamp":1670048208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-93744-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,13]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["93744"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-93744-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,13]]},"assertion":[{"value":"26 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2021","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"}}],"article-number":"14409"}}