{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:28:36Z","timestamp":1790908116126,"version":"4.1.0"},"reference-count":89,"publisher":"PAGEPress Publications","issue":"1","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Histochem"],"abstract":"<jats:p>Ozone (O3) is an oxidizing natural gas widely applied as adjunctive therapeutic treatment for a variety of pathological conditions. Currently, O3-based therapies rely on the low-dose concept i.e., the administration of low O3 concentrations able to induce a mild oxidative stress stimulating antioxidant and anti-inflammatory response without causing cell damage. In addition, low O3\u00a0concentrations are thought to activate cellular and molecular mechanisms responsible for analgesic and regenerative effects. Due to these properties, in the last decade interest has arisen in the fields of orthopedics and regenerative medicine on the potential of O3 to counteract joint diseases involving cartilage degeneration. In this pilot study, we have explored the anti-degenerative potential of O3 on knee articular cartilage explanted from a healthy adult rabbit and maintained in vitro. Light and transmission electron microscopy were used to monitor chondrocyte and extracellular matrix features of cartilage samples undergoing O3 treatment every three days for two weeks. Results demonstrated that low O3 concentrations act on chondrocytes and the molecular components of the extracellular matrix of articular cartilage explants, significantly improving their preservation under in vitro conditions, likely by promoting both protective and pro-regenerative pathways. This opens promising perspectives for further investigations on the therapeutic potential of O3 for the treatment of cartilage degeneration not only as painkilling and anti-inflammatory agent but also as a cartilage regenerative agent.<\/jats:p>","DOI":"10.4081\/ejh.2026.4440","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T14:26:31Z","timestamp":1769437591000},"source":"Crossref","is-referenced-by-count":1,"title":["Low ozone concentrations promote &lt;i&gt;in vitro&lt;\/i&gt; preservation of explanted articular cartilage: an ultrastructural study"],"prefix":"10.4081","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1950-0614","authenticated-orcid":false,"given":"Giada","family":"Remoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7170-9402","authenticated-orcid":false,"given":"Chiara Rita","family":"Inguscio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Boschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Tabaracci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-9232","authenticated-orcid":false,"given":"Manuela","family":"Malatesta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Cisterna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2549","published-online":{"date-parts":[[2026,1,26]]},"reference":[{"key":"47353","doi-asserted-by":"publisher","DOI":"10.1002\/prac.18681050128"},{"key":"47354","doi-asserted-by":"publisher","DOI":"10.1177\/095952875103400117"},{"key":"47355","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-187413300-00031"},{"key":"47356","unstructured":"4. Kellogg JH. Diphtheria: its causes, prevention, and proper treatment. Battle Creek, Good Health Publishing Co.; 1879."},{"key":"47357","doi-asserted-by":"publisher","DOI":"10.2174\/1871529X1502151209114642"},{"key":"47358","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2020.03.026"},{"key":"47359","unstructured":"7. Masan J, Sramka M, Rabarova D. The possibilities of using the effects of ozone therapy in neurology. Neuro Endocrinol Lett 2021;42:13-21."},{"key":"47360","unstructured":"8. Oliveira Modena DA, de Castro Ferreira R, Froes PM, Rocha KC. Ozone therapy for dermatological conditions: a systematic review. J Clin Aesthet Dermatol 2022;15:65-73."},{"key":"47361","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-01976-4"},{"key":"47362","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.840623"},{"key":"47363","doi-asserted-by":"publisher","DOI":"10.3390\/dj11080187"},{"key":"47364","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.14060"},{"key":"47365","doi-asserted-by":"publisher","DOI":"10.3892\/br.2024.1803"},{"key":"47366","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.59855"},{"key":"47367","doi-asserted-by":"publisher","DOI":"10.2174\/0113816128302890240521065453"},{"key":"47368","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-025-05639-6"},{"key":"47369","doi-asserted-by":"publisher","DOI":"10.1016\/j.jebdp.2025.102127"},{"key":"47370","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14072452"},{"key":"47371","doi-asserted-by":"publisher","DOI":"10.1080\/01919512.2012.717847"},{"key":"47372","doi-asserted-by":"publisher","DOI":"10.1186\/2045-9912-1-29"},{"key":"47373","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2015.11.017"},{"key":"47374","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2016.12.035"},{"key":"47375","doi-asserted-by":"publisher","DOI":"10.1155\/2007\/26785"},{"key":"47376","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.12.001"},{"key":"47377","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2017.06.021"},{"key":"47378","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.08.029"},{"key":"47379","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2018.05.093"},{"key":"47380","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252312657"},{"key":"47381","unstructured":"29. Schenk RK, Eggli PS, Hunziker EB. Articular cartilage morphology. In: Kuettner KE, Schleyerbach R, Hascall V, eds. Articular cartilage biochemistry. New York, Raven Press;1986. pp. 3-22."},{"key":"47382","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1996.0320"},{"key":"47383","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1997.19110001.x"},{"key":"47384","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1346.011"},{"key":"47385","doi-asserted-by":"publisher","DOI":"10.1177\/1941738109350438"},{"key":"47386","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S175441"},{"key":"47387","doi-asserted-by":"publisher","DOI":"10.4103\/2045-9912.318859"},{"key":"47388","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2024.1348028"},{"key":"47389","doi-asserted-by":"publisher","DOI":"10.3390\/ijms251910853"},{"key":"47390","doi-asserted-by":"publisher","DOI":"10.1177\/10538127251341834"},{"key":"47391","doi-asserted-by":"publisher","DOI":"10.5812\/aapm-127121"},{"key":"47392","doi-asserted-by":"publisher","DOI":"10.4103\/mgr.MEDGASRES-D-24-00099"},{"key":"47393","unstructured":"41. Javadi Hedayatabad J, Kachooei AR, Taher Chaharjouy N, Vaziri N, Mehrad-Majd H, Emadzadeh M, et al. The effect of ozone (O3) versus hyaluronic acid on pain and function in patients with knee osteoarthritis: a systematic review and meta-analysis. Arch Bone Jt Surg 2020;8:343-54."},{"key":"47394","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S183594"},{"key":"47395","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01184-2"},{"key":"47396","unstructured":"44. Xu W, Zhao X, Sun P, Zhang C, Fu Z, Zhou D. The effect of medical ozone treatment on cartilage chondrocyte autophagy in a rat model of osteoarthritis. Am J Transl Res 2020;12:5967-76."},{"key":"47397","doi-asserted-by":"publisher","DOI":"10.1186\/s13018-022-03233-y"},{"key":"47398","doi-asserted-by":"publisher","DOI":"10.1007\/s00264-020-04871-9"},{"key":"47399","doi-asserted-by":"publisher","DOI":"10.1016\/j.knee.2022.03.003"},{"key":"47400","doi-asserted-by":"publisher","DOI":"10.1016\/j.rvsc.2025.105798"},{"key":"47401","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9100989"},{"key":"47402","doi-asserted-by":"publisher","DOI":"10.1080\/10715760310001604170"},{"key":"47403","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9070775"},{"key":"47404","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2839-3_17"},{"key":"47405","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2013.01.013"},{"key":"47406","unstructured":"54. Mankin HJ, Mow VC, Buckwalter JA, Iannotti JP. Form and function of articular cartilage. In: Simon SR, ed. Orthopaedic basic science. Columbus, American Academy of Orthopaedic Surgeons; 1994. pp. 1-44."},{"key":"47407","unstructured":"55. Lane JM, Brighton CT, Menkowitz BJ. Anaerobic and aerobic metabolism in articular cartilage. J Rheumatol 1977;4:334-42"},{"key":"47408","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1319827"},{"key":"47409","doi-asserted-by":"publisher","DOI":"10.1007\/BF01923509"},{"key":"47410","doi-asserted-by":"publisher","DOI":"10.1016\/0962-8924(94)90069-8"},{"key":"47411","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2024.08.015"},{"key":"47412","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-60037-4"},{"key":"47413","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.02.005"},{"key":"47414","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202309597"},{"key":"47415","doi-asserted-by":"publisher","DOI":"10.1556\/2060.2020.00024"},{"key":"47416","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2014.08.009"},{"key":"47417","doi-asserted-by":"publisher","DOI":"10.1039\/C4RA08997A"},{"key":"47418","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2019.02.217"},{"key":"47419","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163552"},{"key":"47420","doi-asserted-by":"publisher","DOI":"10.1080\/10715769900300431"},{"key":"47421","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110452"},{"key":"47422","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2015.70"},{"key":"47423","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13407"},{"key":"47424","doi-asserted-by":"publisher","DOI":"10.21037\/apm-21-1510"},{"key":"47425","unstructured":"73. Shinmei M, Masuda K, Kikuchi T, Shimomura Y, Okada Y. Production of cytokines by chondrocytes and its role in proteoglycan degradation. J Rheumatol Suppl 1991;27:89-91."},{"key":"47426","doi-asserted-by":"publisher","DOI":"10.3233\/BMR-240023"},{"key":"47427","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-018-4147-6"},{"key":"47428","doi-asserted-by":"publisher","DOI":"10.1097\/PHM.0000000000002343"},{"key":"47429","doi-asserted-by":"publisher","DOI":"10.5114\/reum.2021.110612"},{"key":"47430","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S142755"},{"key":"47431","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108788"},{"key":"47432","doi-asserted-by":"publisher","DOI":"10.1007\/s00590-024-04135-x"},{"key":"47433","doi-asserted-by":"publisher","DOI":"10.1007\/s00167-016-4110-5"},{"key":"47434","doi-asserted-by":"publisher","DOI":"10.3233\/BMR-181294"},{"key":"47435","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-021-04017-x"},{"key":"47436","doi-asserted-by":"publisher","DOI":"10.1177\/10538127251358732"},{"key":"47437","unstructured":"85. Giombini A, Menotti F, Di Cesare A, Giovannangeli F, Rizzo M, Moffa S, Martinelli F. Comparison between intrarticular injection of hyaluronic acid, oxygen ozone, and the combination of both in the treatment of knee osteoarthrosis. J Biol Regul Homeost Agents 2016;30:621-5."},{"key":"47438","doi-asserted-by":"publisher","DOI":"10.3389\/fvets.2020.00265"},{"key":"47439","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctim.2025.103238"},{"key":"47440","unstructured":"88. Latini E, Nusca SM, Curci ER, Lacopo A, Di Stasi V, Santoboni F, et al. Ozone and hyaluronic acid, alone and in combination: exploring temporal dynamics and synergies in intraarticular therapy for knee osteoarthritis. Pain Physician 2025;28:347-57."},{"key":"47441","doi-asserted-by":"publisher","DOI":"10.1016\/j.joms.2025.05.009"}],"container-title":["European Journal of Histochemistry"],"original-title":[],"link":[{"URL":"https:\/\/www.ejh.it\/ejh\/article\/download\/4440\/3639","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ejh.it\/ejh\/article\/download\/4440\/3642","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.ejh.it\/ejh\/article\/download\/4440\/3639","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:03:09Z","timestamp":1770393789000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ejh.it\/ejh\/article\/view\/4440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,26]]},"references-count":89,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,26]]}},"URL":"https:\/\/doi.org\/10.4081\/ejh.2026.4440","relation":{},"ISSN":["2038-8306","1121-760X"],"issn-type":[{"value":"2038-8306","type":"electronic"},{"value":"1121-760X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,1,26]]}}}