{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:25:55Z","timestamp":1785432355676,"version":"3.56.0"},"reference-count":35,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006920","name":"University of Pennsylvania","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006920","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Department of Veterans Affairs Healthcare Network\u2013VISN 4"},{"id":[{"id":"https:\/\/ror.org\/04fhxp168","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"crossref","award":["R21 AR078386"],"award-info":[{"award-number":["R21 AR078386"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"crossref"}]},{"award":["R21 AR078386"],"award-info":[{"award-number":["R21 AR078386"]}],"id":[{"id":"https:\/\/ror.org\/006zn3t30","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Purpose: To determine which age of mice should be used to compare the effects of ADAM8 mutation on intervertebral disc (IVD) responses to injury. Methods: IVDs of ADAM8 mutant (Adam8EQ) and wild type (WT) mice, aged 3, 10 and 18 months were injured. IVD tissues were harvested 1 week post injury for histological and molecular studies. Results: Histological scores increased with aging in intact IVDs, and there were no differences between Adam8EQ and WT mice (n = 11\u201328; p &gt; 0.05). Safranin O-staining was less intense in 10-month than in 3-month-old mice, in both intact and injured IVDs (n = 3\u201315; p &lt; 0.05). Cxcl1, Il6, and Adam8 gene expression levels were higher in the injured tail IVDs of 3-month-old Adam8EQ than WT mice (n = 18\u201330; p &lt; 0.05); the injury-related differences diminished with increasing age. Conclusions: No histological differences were found between Adam8EQ and WT mouse IVDs at 3, 10 or 18 months of age, in the intact or injured discs. The differences in inflammatory marker gene expression were detectable at age 3 months, but were less evident when the injury occurred at age 10 or 18 months. Therefore, to identify differences in injury responses between WT and Adam8EQ mouse IVDs, 3-month-old mice are superior to older mice.<\/jats:p>","DOI":"10.3390\/cells15080730","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T12:01:22Z","timestamp":1776686482000},"page":"730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Age on Intervertebral Disc Tissue Morphology and Gene Expression in the ADAM8-Inactivation Mouse"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0652-2075","authenticated-orcid":false,"given":"Lutian","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Department of Orthopedic Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuozhen","family":"Tian","sequence":"additional","affiliation":[{"name":"Physical Medicine & Rehabilitation, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances S.","family":"Shofer","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Perelman School of Medicine, the University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7484-8800","authenticated-orcid":false,"given":"Yejia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Physical Medicine & Rehabilitation, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Section of Rehabilitation Medicine, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1001\/jama.299.6.656","article-title":"Expenditures and health status among adults with back and neck problems","volume":"299","author":"Martin","year":"2008","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/2045-709X-20-24","article-title":"Does back and neck pain become more common as you get older? A systematic literature review","volume":"20","author":"Fejer","year":"2012","journal-title":"Chiropr. Man. Therap."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mosabbir, A. (2022). Mechanisms behind the Development of Chronic Low Back Pain and Its Neurodegenerative Features. Life, 13.","DOI":"10.3390\/life13010084"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"951","DOI":"10.47162\/RJME.62.4.07","article-title":"Clinical and pathological considerations in lumbar herniated disc associated with inflammatory lesions","volume":"62","author":"Diaconu","year":"2021","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e70021","DOI":"10.1002\/jsp2.70021","article-title":"Contemporary clinical perspectives on chronic low back pain: The biology, mechanics, etc. underpinning clinical and radiological evaluation","volume":"8","author":"Sima","year":"2025","journal-title":"JOR Spine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s12195-009-0072-8","article-title":"Localized Intervertebral Disc Injury Leads to Organ Level Changes in Structure, Cellularity, and Biosynthesis","volume":"2","author":"Iatridis","year":"2009","journal-title":"Cell Mol. Bioeng."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00586-007-0414-y","article-title":"Are animal models useful for studying human disc disorders\/degeneration?","volume":"17","author":"Alini","year":"2008","journal-title":"Eur. Spine J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.1002\/jor.24028","article-title":"Quantitative MRI correlates with histological grade in a percutaneous needle injury mouse model of disc degeneration","volume":"36","author":"Piazza","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/PHM.0000000000000818","article-title":"Intervertebral Disc Degeneration in a Percutaneous Mouse Tail Injury Model","volume":"97","author":"Tian","year":"2018","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1097\/PHM.0000000000001575","article-title":"The Inner Annulus Fibrosus Encroaches on the Nucleus Pulposus in the Injured Mouse Tail Intervertebral Disc","volume":"100","author":"Wei","year":"2021","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ohnishi, T., Sudo, H., Iwasaki, K., Tsujimoto, T., Ito, Y.M., and Iwasaki, N. (2016). In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160486"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Tang, S.N., Walter, B.A., Heimann, M.K., Gantt, C.C., Khan, S.N., Kokiko-Cochran, O.N., Askwith, C.C., and Purmessur, D. (2022). In vivo Mouse Intervertebral Disc Degeneration Models and Their Utility as Translational Models of Clinical Discogenic Back Pain: A Comparative Review. Front. Pain Res., 3.","DOI":"10.3389\/fpain.2022.894651"},{"key":"ref_13","unstructured":"Fox, J.G., Barthold, S., Davisson, M., Newcomer, C.E., Quimby, F.W., and Smith, A. (2007). The-Mouse-in-Biomedical-Research, Elsevier. [2nd ed.]."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1136\/annrheumdis-2016-209428","article-title":"The intervertebral disc contains intrinsic circadian clocks that are regulated by age and cytokines and linked to degeneration","volume":"76","author":"Dudek","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1002\/jor.23634","article-title":"Age-related spontaneous lumbar intervertebral disc degeneration in a mouse model","volume":"36","author":"Ohnishi","year":"2018","journal-title":"J. Orthop. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.bone.2019.03.037","article-title":"Aging of mouse intervertebral disc and association with back pain","volume":"123","author":"Vincent","year":"2019","journal-title":"Bone"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1097\/PHM.0000000000002773","article-title":"Modest Effects of Age on Inflammatory Markers and Histological Features in the Murine Intervertebral Disc Injury Model","volume":"104","author":"Wang","year":"2025","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1097\/BRS.0000000000000397","article-title":"Fibronectin fragments and the cleaving enzyme ADAM-8 in the degenerative human intervertebral disc","volume":"39","author":"Ruel","year":"2014","journal-title":"Spine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1097\/01.brs.0000164097.47091.4c","article-title":"A fibronectin fragment alters the metabolism by rabbit intervertebral disc cells in vitro","volume":"30","author":"Anderson","year":"2005","journal-title":"Spine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1111\/j.1365-2249.2009.04009.x","article-title":"Reduced incidence and severity of experimental autoimmune arthritis in mice expressing catalytically inactive A disintegrin and metalloproteinase 8 (ADAM8)","volume":"158","author":"Zack","year":"2009","journal-title":"Clin. Exp. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"101059","DOI":"10.1016\/j.gendis.2023.06.028","article-title":"ADAM8 inactivation retards intervertebral disc degeneration in mice","volume":"11","author":"Tian","year":"2023","journal-title":"Genes. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1038\/s41598-021-81495-y","article-title":"Elevated inflammatory gene expression in intervertebral disc tissues in mice with ADAM8 inactivated","volume":"11","author":"Zhang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1097\/PHM.0000000000002278","article-title":"Tnfa, Il6, Cxcl1, and Adam8 Genes Are the Early Markers After Mouse Tail Intervertebral Disc Injury","volume":"102","author":"Lu","year":"2023","journal-title":"Am. J. Phys. Med. Rehabil."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Mierke, C.T. (2023). The versatile roles of ADAM8 in cancer cell migration, mechanics, and extracellular matrix remodeling. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1130823"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0378-1119(94)90060-4","article-title":"Rules and guidelines for nomenclature of mouse genes. International Committee on Standardized Genetic Nomenclature for Mice","volume":"147","author":"Davisson","year":"1994","journal-title":"Gene"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1164","DOI":"10.1002\/jsp2.1164","article-title":"Development of a standardized histopathology scoring system using machine learning algorithms for intervertebral disc degeneration in the mouse model-An ORS spine section initiative","volume":"4","author":"Melgoza","year":"2021","journal-title":"JOR Spine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.2106\/00004623-197153010-00007","article-title":"Chemical basis for the histological use of safranin O in the study of articular cartilage","volume":"53","author":"Rosenberg","year":"1971","journal-title":"J. Bone Joint Surg. Am."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13006","DOI":"10.1111\/acel.13006","article-title":"Chondrocyte-like nested cells in the aged intervertebral disc are late-stage nucleus pulposus cells","volume":"18","author":"Mohanty","year":"2019","journal-title":"Aging Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e70127","DOI":"10.1002\/jsp2.70127","article-title":"Injury Induces More Severe Biomechanical Changes in Middle-Aged and Geriatric Lumbar Spines in a Mouse Ex Vivo Model","volume":"8","author":"Bhadouria","year":"2025","journal-title":"JOR Spine"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1016\/j.joca.2020.06.009","article-title":"Severity of intervertebral disc herniation regulates cytokine and chemokine levels in patients with chronic radicular back pain","volume":"28","author":"Jacobsen","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.pain.2004.12.015","article-title":"Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica","volume":"114","author":"Virtanen","year":"2005","journal-title":"Pain"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.3892\/etm.2016.3079","article-title":"Elevated interleukin-6 expression levels are associated with intervertebral disc degeneration","volume":"11","author":"Deng","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Korbecki, J., Gassowska-Dobrowolska, M., Wojcik, J., Szatkowska, I., Barczak, K., Chlubek, M., and Baranowska-Bosiacka, I. (2022). The Importance of CXCL1 in Physiology and Noncancerous Diseases of Bone, Bone Marrow, Muscle and the Nervous System. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23084205"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e1252","DOI":"10.1002\/jsp2.1252","article-title":"Analysis of intervertebral disc CCR6 and IL-6 gene levels with short-term postoperative low back pain after spinal fusion in lumbar degenerative disease","volume":"6","author":"Hiyama","year":"2023","journal-title":"JOR Spine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"131","DOI":"10.30802\/AALAS-CM-19-000034","article-title":"Influence of Genetic Background and Sex on Gene Expression in the Mouse (Mus musculus) Tail in a Model of Intervertebral Disc Injury","volume":"70","author":"Brent","year":"2020","journal-title":"Comp. Med."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/8\/730\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:17:11Z","timestamp":1776831431000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/8\/730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["cells15080730"],"URL":"https:\/\/doi.org\/10.3390\/cells15080730","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}