{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T07:07:21Z","timestamp":1782803241174,"version":"3.54.5"},"reference-count":44,"publisher":"Portland Press Ltd.","issue":"9","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Objectives: In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties.<\/jats:p>\n               <jats:p>Methods: A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention.<\/jats:p>\n               <jats:p>Results: In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not.<\/jats:p>\n               <jats:p>Conclusion: Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints.<\/jats:p>","DOI":"10.1042\/bsr20194207","type":"journal-article","created":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T11:40:55Z","timestamp":1597664455000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Microstructure and mechanical properties of subchondral bone are negatively regulated by tramadol in osteoarthritis in mice"],"prefix":"10.1042","volume":"40","author":[{"given":"Chen-Chen","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, P.R. China"},{"name":"Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, Jiangsu, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, P.R. China"},{"name":"Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, Jiangsu, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Jie","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liang","sequence":"additional","affiliation":[{"name":"Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, Jiangsu, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua-Ye","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, P.R. China"},{"name":"Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, Jiangsu, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Dong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0617-2597","authenticated-orcid":false,"given":"Zong-Ping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou 215006, Jiangsu, P.R. China"},{"name":"Orthopedic Institute, Soochow University, 708 Renmin Road, Suzhou 215006, Jiangsu, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,9,4]]},"reference":[{"key":"2021111620254380200_B1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.2174\/1573397115666190214164407","article-title":"Novel herbal topical patch containing Curcumin and Arnica Montana for the treatment of osteoarthritis","volume":"16","author":"Kriplani","year":"2019","journal-title":"Curr. Rheumatol. Rev."},{"key":"2021111620254380200_B2","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.biopha.2018.11.141","article-title":"Chronic exposure to the opioid tramadol induces oxidative damage, inflammation and apoptosis, and alters cerebral monoamine neurotransmitters in rats","volume":"110","author":"Mohamed","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"2021111620254380200_B3","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/art.39465","article-title":"The prevalence of symptomatic knee osteoarthritis in china: results from the china health and retirement longitudinal study","volume":"68","author":"Tang","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"2021111620254380200_B4","article-title":"Osteoarthritis: care and management in adults","author":"National Institute for Health and Clinical Excellence (NICE)","year":"2014","journal-title":"Natl. Inst. Clin. Excel."},{"key":"2021111620254380200_B5","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1111\/j.1476-5381.1992.tb14226.x","article-title":"Interaction of the central analgesic, tramadol, with the uptake and release of 5-hydroxytryptamine in the rat brain in vitro","volume":"105","author":"Driessen","year":"1992","journal-title":"Br. J. Pharmacol."},{"key":"2021111620254380200_B6","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S0278-5846(99)00010-X","article-title":"Effect of acute and chronic tramadol on [3h]-norepinephrine-uptake in rat cortical synaptosomes","volume":"23","author":"Franceschini","year":"1999","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"2021111620254380200_B7","first-page":"275","article-title":"Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an \u2018atypical\u2019 opioid analgesic","volume":"260","author":"Raffa","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2021111620254380200_B8","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1093\/ajhp\/54.6.643","article-title":"Tramadol: a new centrally acting analgesic","volume":"54","author":"Lewis","year":"1997","journal-title":"Am. J. Health Syst. Pharm."},{"key":"2021111620254380200_B9","first-page":"CD005522","article-title":"Tramadol for osteoarthritis","volume":"3","author":"Cepeda","year":"2006","journal-title":"Cochrane Database Syst. Rev."},{"key":"2021111620254380200_B10","first-page":"571","article-title":"Treatment of osteoarthritis of the knee: evidence-based guideline, 2nd edition","volume":"21","author":"Jevsevar","year":"2013","journal-title":"J. Am. Acad. Orthop. Surg."},{"key":"2021111620254380200_B11","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1002\/acr.21596","article-title":"American College of Rheumatology 2012 recommendations for the use of nonpharmacologic and pharmacologic therapies in osteoarthritis of the hand, hip, and knee","volume":"64","author":"Hochberg","year":"2012","journal-title":"Arthritis Care Res. (Hoboken)"},{"key":"2021111620254380200_B12","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1002\/acr.22360","article-title":"Trends in prescription of opioids from 2003\u20132009 in persons with knee osteoarthritis","volume":"66","author":"Wright","year":"2014","journal-title":"Arthritis Care Res. (Hoboken)"},{"key":"2021111620254380200_B13","doi-asserted-by":"publisher","first-page":"e0175565","DOI":"10.1371\/journal.pone.0175565","article-title":"Analgesic efficacy of tramadol in cats with naturally occurring osteoarthritis","volume":"12","author":"Monteiro","year":"2017","journal-title":"PLoS ONE"},{"key":"2021111620254380200_B14","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1002\/acr.22916","article-title":"Cost-effectiveness of tramadol and oxycodone in the treatment of knee osteoarthritis","volume":"69","author":"Smith","year":"2016","journal-title":"Arthritis Care Res. (Hoboken)"},{"key":"2021111620254380200_B15","doi-asserted-by":"publisher","first-page":"565","DOI":"10.2460\/javma.252.5.565","article-title":"Evaluation of tramadol for treatment of osteoarthritis in geriatric cats","volume":"252","author":"Guedes","year":"2018","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"2021111620254380200_B16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1159\/000054586","article-title":"Expression of opioid receptors in osteoblast-like mg-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells","volume":"72","author":"P\u00c9Rez-Castrill\u00d3N","year":"2000","journal-title":"Neuroendocrinology"},{"key":"2021111620254380200_B17","doi-asserted-by":"publisher","first-page":"30985","DOI":"10.1038\/srep30985","article-title":"Peripheral serotonin-mediated system suppresses bone development and regeneration via serotonin 6 g-protein-coupled receptor","volume":"6","author":"Yun","year":"2016","journal-title":"Sci. Rep."},{"key":"2021111620254380200_B18","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.bone.2018.08.019","article-title":"Long term time trends in use of medications associated with risk of developing osteoporosis: nationwide data for Denmark from 1999 to 2016","volume":"120","author":"Skj\u00f8dt","year":"2019","journal-title":"Bone"},{"key":"2021111620254380200_B19","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.joca.2007.03.006","article-title":"The surgical destabilization of the medial meniscus (dmm) model of osteoarthritis in the 129\/svev mouse","volume":"15","author":"Glasson","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111620254380200_B20","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/978-1-4939-8997-3_15","article-title":"Osteoarthritis mouse model of destabilization of the medial meniscus","volume":"1914","author":"Sophocleous","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"2021111620254380200_B21","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1017\/S1461145709000236","article-title":"Cooperative opioid and serotonergic mechanisms generate superior antidepressant-like effects in a mice model of depression","volume":"12","author":"Berrocoso","year":"2009","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"2021111620254380200_B22","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.spinee.2018.10.018","article-title":"Controlled immobilization-traction based on intervertebral stability is conducive to the regeneration or repair of the degenerative disc: an in vivo study on the rat coccygeal model","volume":"19","author":"Che","year":"2019","journal-title":"Spine J."},{"key":"2021111620254380200_B23","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/jbmr.141","article-title":"Guidelines for assessment of bone microstructure in rodents using micro\u2013computed tomography","volume":"25","author":"Bouxsein","year":"2010","journal-title":"J. Bone Miner. Res."},{"key":"2021111620254380200_B24","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.bone.2019.05.010","article-title":"SDF-1\/CXCR4 axis coordinates crosstalk between subchondral bone and articular cartilage in osteoarthritis pathogenesis","volume":"125","author":"Qin","year":"2019","journal-title":"Bone"},{"key":"2021111620254380200_B25","doi-asserted-by":"publisher","first-page":"S66","DOI":"10.1016\/j.joca.2010.04.017","article-title":"The OARSI histopathology initiative\u2013recommendations for histological assessments of osteoarthritis in the dog","volume":"18","author":"Cook","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111620254380200_B26","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1016\/j.joca.2011.04.011","article-title":"Acute joint pathology and synovial inflammation is associated with increased intra-articular fracture severity in the mouse knee","volume":"19","author":"Lewis","year":"2011","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111620254380200_B27","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1177\/0022034510377791","article-title":"Aging and bone","volume":"89","author":"Boskey","year":"2010","journal-title":"J. Dent. Res."},{"key":"2021111620254380200_B28","doi-asserted-by":"publisher","first-page":"1193","DOI":"10.1002\/art.20124","article-title":"The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model","volume":"50","author":"Hayami","year":"2004","journal-title":"Arthritis Rheum."},{"key":"2021111620254380200_B29","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1016\/j.joca.2014.05.023","article-title":"Bone\u2013cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies","volume":"22","author":"Yuan","year":"2014","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111620254380200_B30","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1016\/j.joca.2018.02.905","article-title":"Subchondral trabecular bone integrity changes following acl injury and reconstruction: a cohort study with a nested, matched case-control analysis","volume":"26","author":"Birch","year":"2018","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111620254380200_B31","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.joca.2018.12.006","article-title":"The role of subchondral bone, and its histomorphology, on the dynamic viscoelasticity of cartilage, bone and osteochondral cores","volume":"27","author":"Fell","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111620254380200_B32","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s12917-019-1960-3","article-title":"Safety and efficacy of reduced dosage ketoprofen with or without tramadol for long-term treatment of osteoarthritis in dogs: a randomized clinical trial","volume":"15","author":"Monteiro","year":"2019","journal-title":"BMC Vet. Res."},{"key":"2021111620254380200_B33","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1080\/03007995.2017.1310092","article-title":"Multimodal analgesia in moderate-to-severe pain: a role for a new fixed combination of dexketoprofen and tramadol","volume":"33","author":"Varrassi","year":"2017","journal-title":"Curr. Med. Res. Opin."},{"key":"2021111620254380200_B34","doi-asserted-by":"publisher","first-page":"3578.e1","DOI":"10.1016\/j.arth.2017.07.030","article-title":"Are we still prescribing opioids for osteoarthritis","volume":"32","author":"DeMik","year":"2017","journal-title":"J. Arthroplasty"},{"key":"2021111620254380200_B35","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1186\/s13075-019-2004-x","article-title":"Factors related to the use of opioids as early treatment in patients with knee osteoarthritis","volume":"21","author":"Cho","year":"2019","journal-title":"Arthritis Res. Ther."},{"key":"2021111620254380200_B36","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1016\/j.joca.2015.04.015","article-title":"Effects of short-term gentle treadmill walking on subchondral bone in a rat model of instability-induced osteoarthritis","volume":"23","author":"Iijima","year":"2015","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111620254380200_B37","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/nrrheum.2013.72","article-title":"Post-traumatic osteoarthritis: from mouse models to clinical trials","volume":"9","author":"Little","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"2021111620254380200_B38","doi-asserted-by":"publisher","first-page":"2690","DOI":"10.1002\/art.30307","article-title":"Osteoarthritis induction leads to early and temporal subchondral plate porosity in the tibial plateau of mice: an in vivo microfocal computed tomography study","volume":"63","author":"Botter","year":"2011","journal-title":"Arthritis Rheum."},{"key":"2021111620254380200_B39","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1016\/j.joca.2015.11.005","article-title":"Subchondral and epiphyseal bone remodeling following surgical transection and noninvasive rupture of the anterior cruciate ligament as models of post-traumatic osteoarthritis","volume":"24","author":"Maerz","year":"2016","journal-title":"Osteoarthritis Cartilage"},{"key":"2021111620254380200_B40","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1002\/jor.23132","article-title":"Attenuation of cartilage degeneration by calcitonin gene-related paptide receptor antagonist via inhibition of subchondral bone sclerosis in osteoarthritis mice","volume":"34","author":"Nakasa","year":"2016","journal-title":"J. Orthop. Res."},{"key":"2021111620254380200_B41","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3736\/jintegrmed2013004","article-title":"A comparison of kneipp hydrotherapy with conventional physiotherapy in the treatment of osteoarthritis: a pilot trial","volume":"11","author":"Schencking","year":"2013","journal-title":"J. Integr. Med."},{"key":"2021111620254380200_B42","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1159\/000054586","article-title":"Expression of opioid receptors in osteoblast-like mg-63 cells, and effects of different opioid agonists on alkaline phosphatase and osteocalcin secretion by these cells","volume":"72","author":"P\u00c9Rez-Castrill\u00d3N","year":"2000","journal-title":"Neuroendocrinology"},{"key":"2021111620254380200_B43","doi-asserted-by":"publisher","first-page":"30985","DOI":"10.1038\/srep30985","article-title":"Peripheral serotonin-mediated system suppresses bone development and regeneration via serotonin 6 g-protein-coupled receptor","volume":"6","author":"Yun","year":"2016","journal-title":"Sci. Rep."},{"key":"2021111620254380200_B44","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1111\/j.1365-2559.2006.02508.x","article-title":"Synovitis score: discrimination between chronic low-grade and high-grade synovitis","volume":"49","author":"Krenn","year":"2006","journal-title":"Histopathology"}],"container-title":["Bioscience Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20194207\/892351\/bsr-2019-4207.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/bioscirep\/article-pdf\/doi\/10.1042\/BSR20194207\/892351\/bsr-2019-4207.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T20:54:48Z","timestamp":1637096088000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/bioscirep\/article\/40\/9\/BSR20194207\/226099\/Microstructure-and-mechanical-properties-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":44,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9,30]]}},"URL":"https:\/\/doi.org\/10.1042\/bsr20194207","relation":{},"ISSN":["0144-8463","1573-4935"],"issn-type":[{"value":"0144-8463","type":"print"},{"value":"1573-4935","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9]]},"published":{"date-parts":[[2020,9]]},"article-number":"BSR20194207"}}