{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:10:35Z","timestamp":1792599035694,"version":"4.5.0"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"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":["Inflammopharmacol"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Novel treatment strategies are urgently required for osteoarthritis (OA). Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and elucidate the molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague\u2013Dawley rats. The experimental animals were divided into normal control group (injected with saline\u2009+\u2009treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA\u2009+\u2009treated with PBS, CON), 50 or 100\u00a0mg\/kg body weight (BW)\/day PEA-treated group (injected with MIA\u2009+\u2009treated with 50 or 100\u00a0mg of PEA\/kg BW\/day, PEA50 or PEA100), and positive control group (injected with MIA\u2009+\u2009treated with 6\u00a0mg of diclofenac\/kg BW\/day, DiC). The changes in blood parameters, body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. Oral administration of PEA had no adverse effects on the BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-\u03b1, interleukin (IL)-1\u03b2, and prostaglandin E2 considerably reduced in the PEA100 group compared with those in the CON group. In the synovia of knee joints, the mRNA expression of <jats:italic>iNOS<\/jats:italic>, <jats:italic>5-Lox<\/jats:italic>, <jats:italic>Cox-2<\/jats:italic>, <jats:italic>Il-1\u03b2<\/jats:italic>, <jats:italic>Tnf-\u03b1<\/jats:italic>, and <jats:italic>Mmp-2<\/jats:italic>, <jats:italic>-3<\/jats:italic>, <jats:italic>-9<\/jats:italic>, and <jats:italic>-13<\/jats:italic> apparently increased with MIA administration. Meanwhile, <jats:italic>Timp-1<\/jats:italic> mRNA expression apparently decreased in the CON group but increased to the normal level with PEA treatment. Thus, PEA can be an effective therapeutic agent for OA.<\/jats:p>","DOI":"10.1007\/s10787-021-00870-3","type":"journal-article","created":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T15:02:50Z","timestamp":1630508570000},"page":"1475-1486","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Anti-inflammatory activity of palmitoylethanolamide ameliorates osteoarthritis induced by monosodium iodoacetate in Sprague\u2013Dawley rats"],"prefix":"10.1007","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4475-1434","authenticated-orcid":false,"given":"Jae In","family":"Jung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8642-1978","authenticated-orcid":false,"given":"Hyun Sook","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7312-8545","authenticated-orcid":false,"given":"Young Eun","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0174-3485","authenticated-orcid":false,"given":"So Mi","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7440-6105","authenticated-orcid":false,"given":"Su Hee","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-9620","authenticated-orcid":false,"given":"Joo Myung","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2171-6847","authenticated-orcid":false,"given":"Cho Young","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6045-9927","authenticated-orcid":false,"given":"Yoon Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9305-4769","authenticated-orcid":false,"given":"Eun Ji","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,1]]},"reference":[{"key":"870_CR1","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1016\/j.drudis.2014.06.007","volume":"19","author":"M Alhouayek","year":"2014","unstructured":"Alhouayek M, Muccioli GG (2014) Harnessing the anti-inflammatory potential of palmitoylethanolamide. Drug Discov Today 19:1632\u20131639. https:\/\/doi.org\/10.1016\/j.drudis.2014.06.007","journal-title":"Drug Discov Today"},{"key":"870_CR2","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1007\/s10787-019-00584-7","volume":"27","author":"M Alsalem","year":"2019","unstructured":"Alsalem M, Haddad M, Aldossary SA, Kalbouneh H, Altarifi A, Jaffal SM, Abbas MA, Aldaoud N, El-Salem K (2019) Role of cannabinoid receptor 1 and the peroxisome proliferator-activated receptor \u03b1 in mediating anti-nociceptive effects of synthetic cannabinoids and a cannabinoid-like compound. Inflammopharmacology 27:1131\u20131142. https:\/\/doi.org\/10.1007\/s10787-019-00584-7","journal-title":"Inflammopharmacology"},{"key":"870_CR3","doi-asserted-by":"publisher","first-page":"85","DOI":"10.12816\/0006075","volume":"8","author":"AM Alshami","year":"2014","unstructured":"Alshami AM (2014) Knee osteoarthritis related pain: a narrative review of diagnosis and treatment. Int J Health Sci (qassim) 8:85\u2013104. https:\/\/doi.org\/10.12816\/0006075","journal-title":"Int J Health Sci (qassim)"},{"key":"870_CR4","first-page":"403","volume":"65","author":"S Audial","year":"2015","unstructured":"Audial S, Bonnotte B (2015) Inflammation. Rev Prat 65:403\u2013408","journal-title":"Rev Prat"},{"key":"870_CR5","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.ejpain.2006.02.013","volume":"11","author":"JM Bjordal","year":"2007","unstructured":"Bjordal JM, Klovning A, Ljunggren AE, Sl\u00f8rdal L (2007) Short-term efficacy of pharmacotherapeutic interventions in osteoarthritic knee pain: a meta-analysis of randomised placebo-controlled trials. Eur J Pain 11:125\u2013138. https:\/\/doi.org\/10.1016\/j.ejpain.2006.02.013","journal-title":"Eur J Pain"},{"key":"870_CR6","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1186\/s12917-017-1151-z","volume":"13","author":"D Britti","year":"2017","unstructured":"Britti D, Crupi R, Impellizzeri D, Gugliandolo E, Fusco R, Schievano C, Morittu VM, Evangelista M, Di Paola R, Cuzzocrea S (2017) A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models. BMC Vet Res 13:229. https:\/\/doi.org\/10.1186\/s12917-017-1151-z","journal-title":"BMC Vet Res"},{"key":"870_CR7","doi-asserted-by":"publisher","first-page":"39762","DOI":"10.1074\/jbc.M303541200","volume":"278","author":"C Chadjichristos","year":"2003","unstructured":"Chadjichristos C, Ghayor C, Kypriotou M, Martin G, Renard E, Ala-Kokko L, Suske G, de Crombrugghe B, Pujol JP, Gal\u00e9ra P (2003) Sp1 and Sp3 transcription factors mediate interleukin-1 beta down-regulation of human type II collagen gene expression in articular chondrocytes. J Biol Chem 278:39762\u201339772. https:\/\/doi.org\/10.1074\/jbc.M303541200","journal-title":"J Biol Chem"},{"key":"870_CR8","doi-asserted-by":"publisher","first-page":"16044","DOI":"10.1038\/boneres.2016.44","volume":"5","author":"D Chen","year":"2017","unstructured":"Chen D, Shen J, Zhao W, Wang T, Han L, Hamilton JL, Im HJ (2017) Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res 5:16044. https:\/\/doi.org\/10.1038\/boneres.2016.44","journal-title":"Bone Res"},{"key":"870_CR9","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.joca.2011.03.010","volume":"19","author":"S Clockaerts","year":"2011","unstructured":"Clockaerts S, Bastiaansen-Jenniskens YM, Feijt C, Verhaar JA, Somville J, De Clerck LS, Van Osch GJ (2011) Peroxisome proliferator activated receptor alpha activation decreases inflammatory and destructive responses in osteoarthritic cartilage. Osteoarthritis Cartilage 19:895\u2013902. https:\/\/doi.org\/10.1016\/j.joca.2011.03.010","journal-title":"Osteoarthritis Cartilage"},{"key":"870_CR10","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.pain.2008.06.003","volume":"139","author":"B Costa","year":"2008","unstructured":"Costa B, Comelli F, Bettoni I, Colleoni M, Giagnoni G (2008) The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors. Pain 139:541\u2013550. https:\/\/doi.org\/10.1016\/j.pain.2008.06.003","journal-title":"Pain"},{"key":"870_CR11","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1016\/j.neuropharm.2005.01.001","volume":"48","author":"NA Darmani","year":"2005","unstructured":"Darmani NA, Izzo AA, Degenhardt B, Valenti M, Scaglione G, Capasso R, Sorrentini I, Di Marzo V (2005) Involvement of the cannabimimetic compound, N-palmitoyl-ethanolamine, in inflammatory and neuropathic conditions: review of the available pre-clinical data, and first human studies. Neuropharmacology 48:1154\u20131163. https:\/\/doi.org\/10.1016\/j.neuropharm.2005.01.001","journal-title":"Neuropharmacology"},{"key":"870_CR12","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.2174\/138920111798357320","volume":"12","author":"WN D'Souza","year":"2011","unstructured":"D\u2019Souza WN, Ng GY, Youngblood BD, Tsuji W, Lehto SG (2011) A review of current animal models of osteoarthritis pain. Curr Pharm Biotechnol 12:1596\u20131612. https:\/\/doi.org\/10.2174\/138920111798357320","journal-title":"Curr Pharm Biotechnol"},{"key":"870_CR13","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1002\/1529-0131(200103)44:3<595::AID-ANR108>3.0.CO;2-8","volume":"44","author":"H Fahmi","year":"2001","unstructured":"Fahmi H, Di Battista JA, Pelletier JP, Mineau F, Ranger P, Martel-Pelletier J (2001) Peroxisome proliferator\u2013activated receptor gamma activators inhibit interleukin-1beta-induced nitric oxide and matrix metalloproteinase 13 production in human chondrocytes. Arthritis Rheum 44:595\u2013607. https:\/\/doi.org\/10.1002\/1529-0131(200103)44:3%3c595::AID-ANR108%3e3.0.CO;2-8","journal-title":"Arthritis Rheum"},{"key":"870_CR14","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/papr.12551","volume":"17","author":"M Fusco","year":"2017","unstructured":"Fusco M, Skaper SD, Coaccioli S, Varrassi G, Paladini A (2017) Degenerative joint diseases and neuroinflammation. Pain Pract 17:522\u2013532. https:\/\/doi.org\/10.1111\/papr.12551","journal-title":"Pain Pract"},{"key":"870_CR15","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1111\/j.1526-4637.2012.01432.x","volume":"13","author":"A Gatti","year":"2012","unstructured":"Gatti A, Lazzari M, Gianfelice V, Di Paolo A, Sabato E, Sabato AF (2012) Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis. Pain Med 13:1121\u20131130. https:\/\/doi.org\/10.1111\/j.1526-4637.2012.01432.x","journal-title":"Pain Med"},{"key":"870_CR16","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.1016\/j.joca.2010.05.025","volume":"18","author":"SS Glasson","year":"2010","unstructured":"Glasson SS, Chambers MG, van Den Berg WB, Little CB (2010) The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthr Cartil 18:S17\u2013S23. https:\/\/doi.org\/10.1016\/j.joca.2010.05.025","journal-title":"Osteoarthr Cartil"},{"key":"870_CR17","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41598-017-00342-1","volume":"7","author":"F Guida","year":"2017","unstructured":"Guida F, Luongo L, Boccella S et al (2017) Palmitoylethanolamide induces microglia changes associated with increased migration and phagocytic activity: involvement of the CB2 receptor. Sci Rep 7:375. https:\/\/doi.org\/10.1038\/s41598-017-00342-1","journal-title":"Sci Rep"},{"key":"870_CR18","doi-asserted-by":"publisher","first-page":"437","DOI":"10.2147\/JPR.S32143","volume":"5","author":"JM Hesselink","year":"2012","unstructured":"Hesselink JM, Hekker TA (2012) Therapeutic utility of palmitoylethanolamide in the treatment of neuropathic pain associated with various pathological conditions: a case series. J Pain Res 5:437\u2013442. https:\/\/doi.org\/10.2147\/JPR.S32143","journal-title":"J Pain Res"},{"key":"870_CR19","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1097\/01.hco.0000136130.95746.14","volume":"16","author":"B Hinz","year":"2004","unstructured":"Hinz B, Brune K (2004) Pain and osteoarthritis: new drugs and mechanisms. Curr Opin Rheumatol 16:628\u2013633. https:\/\/doi.org\/10.1097\/01.hco.0000136130.95746.14","journal-title":"Curr Opin Rheumatol"},{"key":"870_CR20","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1002\/acr.20142","volume":"62","author":"JR Hochman","year":"2010","unstructured":"Hochman JR, French MR, Bermingham SL, Hawker GA (2010) The nerve of osteoarthritis pain. Arthritis Care Res (hoboken) 62:1019\u20131023. https:\/\/doi.org\/10.1002\/acr.20142","journal-title":"Arthritis Care Res (hoboken)"},{"key":"870_CR21","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1007\/s12031-016-0775-y","volume":"59","author":"D Huang","year":"2016","unstructured":"Huang D, Zhao Q, Liu H, Guo Y, Xu H (2016) PPAR-\u03b1 Agonist WY-14643 Inhibits LPS-Induced Inflammation in Synovial Fibroblasts via NF-kB Pathway. J Mol Neurosci 59:544\u2013553. https:\/\/doi.org\/10.1007\/s12031-016-0775-y","journal-title":"J Mol Neurosci"},{"key":"870_CR22","doi-asserted-by":"publisher","first-page":"R192","DOI":"10.1186\/ar4382","volume":"15","author":"D Impellizzeri","year":"2013","unstructured":"Impellizzeri D, Esposito E, Di Paola R, Ahmad A, Campolo M, Peli A, Morittu VM, Britti D, Cuzzocrea S (2013) Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection of collagen type II in mice. Arthritis Res Ther 15:R192. https:\/\/doi.org\/10.1186\/ar4382","journal-title":"Arthritis Res Ther"},{"key":"870_CR23","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13018-016-0346-5","volume":"11","author":"EL Kuyinu","year":"2016","unstructured":"Kuyinu EL, Narayanan G, Nair LS, Laurencin CT (2016) Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res 11:19. https:\/\/doi.org\/10.1186\/s13018-016-0346-5","journal-title":"J Orthop Surg Res"},{"key":"870_CR24","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1111\/ejn.12468","volume":"39","author":"C La Porta","year":"2014","unstructured":"La Porta C, Bura SA, Negrete R, Maldonado R (2014) Involvement of the endocannabinoid system in osteoarthritis pain. Eur J Neurosci 39:485\u2013500. https:\/\/doi.org\/10.1111\/ejn.12468","journal-title":"Eur J Neurosci"},{"key":"870_CR25","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/j.lfs.2005.05.012","volume":"77","author":"J LoVerme","year":"2005","unstructured":"LoVerme J, La Rana G, Russo R, Calignano A, Piomelli D (2005) The search for the palmitoylethanolamide receptor. Life Sci 77:1685\u20131698. https:\/\/doi.org\/10.1016\/j.lfs.2005.05.012","journal-title":"Life Sci"},{"key":"870_CR26","first-page":"37","volume":"7","author":"GS Man","year":"2014","unstructured":"Man GS, Mologhianu G (2014) Osteoarthritis pathogenesis: a complex process that involves the entire joint. J Med Life 7:37\u201341","journal-title":"J Med Life"},{"key":"870_CR27","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1080\/14656566.2017.1414802","volume":"19","author":"KH Maniar","year":"2018","unstructured":"Maniar KH, Jones IA, Gopalakrishna R, Vangsness CT (2018) Lowering side effects of NSAID usage in osteoarthritis: recent attempts at minimizing dosage. Expert Opin Pharmacother 19:93\u2013102. https:\/\/doi.org\/10.1080\/14656566.2017.1414802","journal-title":"Expert Opin Pharmacother"},{"key":"870_CR28","doi-asserted-by":"publisher","first-page":"2189","DOI":"10.2147\/JPR.S154002","volume":"11","author":"JC Mora","year":"2018","unstructured":"Mora JC, Przkora R, Cruz-Almeida Y (2018) Knee osteoarthritis: pathophysiology and current treatment modalities. J Pain Res 11:2189\u20132196. https:\/\/doi.org\/10.2147\/JPR.S154002","journal-title":"J Pain Res"},{"key":"870_CR29","doi-asserted-by":"publisher","first-page":"11","DOI":"10.36076\/ppj\/2016.19.11","volume":"19","author":"A Paladini","year":"2016","unstructured":"Paladini A, Fusco M, Cenacchi T, Schievano C, Piroli A, Varrassi G (2016) Palmitoylethanolamide, a special food for medical purposes, in the treatment of chronic pain: a pooled data meta-analysis. Pain Physician 19:11\u201324","journal-title":"Pain Physician"},{"key":"870_CR30","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1111\/bph.13580","volume":"174","author":"S Petrosino","year":"2017","unstructured":"Petrosino S, Di Marzo V (2017) The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations. Br J Pharmacol 174:1349\u20131365. https:\/\/doi.org\/10.1111\/bph.13580","journal-title":"Br J Pharmacol"},{"key":"870_CR31","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.joca.2005.07.014","volume":"14","author":"KP Pritzker","year":"2006","unstructured":"Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB (2006) Osteoarthritis cartilage histopathology: grading and staging. Osteoarthr Cartil 14:13\u201329. https:\/\/doi.org\/10.1016\/j.joca.2005.07.014","journal-title":"Osteoarthr Cartil"},{"key":"870_CR32","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.tvjl.2005.10.003","volume":"173","author":"G Re","year":"2007","unstructured":"Re G, Barbero R, Miolo A, Di Marzo V (2007) Palmitoylethanolamide, endocannabinoids and related cannabimimetic compounds in protection against tissue inflammation and pain: potential use in companion animals. Vet J 173:21\u201330. https:\/\/doi.org\/10.1016\/j.tvjl.2005.10.003","journal-title":"Vet J"},{"key":"870_CR33","doi-asserted-by":"publisher","first-page":"R43","DOI":"10.1186\/ar2401","volume":"10","author":"D Richardson","year":"2008","unstructured":"Richardson D, Pearson RG, Kurian N, Latif ML, Garle MJ, Barrett DA, Kendall DA, Scammell BE, Reeve AJ, Chapman V (2008) Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Res Ther 10:R43. https:\/\/doi.org\/10.1186\/ar2401","journal-title":"Arthritis Res Ther"},{"key":"870_CR34","doi-asserted-by":"publisher","first-page":"35523","DOI":"10.1074\/jbc.M106038200","volume":"276","author":"D Rontein","year":"2001","unstructured":"Rontein D, Nishida I, Tashiro G, Yoshioka K, Wu WI, Voelker DR, Basset G, Hanson AD (2001) Plants synthesize ethanolamine by direct decarboxylation of serine using a pyridoxal phosphate enzyme. J Biol Chem 276:35523\u201335529. https:\/\/doi.org\/10.1074\/jbc.M106038200","journal-title":"J Biol Chem"},{"key":"870_CR35","doi-asserted-by":"publisher","first-page":"3666","DOI":"10.1002\/art.27698","volume":"62","author":"DR Sagar","year":"2010","unstructured":"Sagar DR, Staniaszek LE, Okine BN et al (2010) Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain. Arthritis Rheum 62:3666\u20133676. https:\/\/doi.org\/10.1002\/art.27698","journal-title":"Arthritis Rheum"},{"key":"870_CR36","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/322547a0","volume":"322","author":"J Saklatvala","year":"1986","unstructured":"Saklatvala J (1986) Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature 322:547\u2013549. https:\/\/doi.org\/10.1038\/322547a0","journal-title":"Nature"},{"key":"870_CR37","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1007\/s00253-007-0932-x","volume":"75","author":"E Scott","year":"2007","unstructured":"Scott E, Peter F, Sanders J (2007) Biomass in the manufacture of industrial products\u2013the use of proteins and amino acids. Appl Microbiol Biotechnol 75:751\u2013762. https:\/\/doi.org\/10.1007\/s00253-007-0932-x","journal-title":"Appl Microbiol Biotechnol"},{"key":"870_CR38","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/s10787-019-00582-9","volume":"27","author":"E Steels","year":"2019","unstructured":"Steels E, Venkatesh R, Steels E, Vitetta G, Vitetta L (2019) A double-blind randomized placebo controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology 27:475\u2013485. https:\/\/doi.org\/10.1007\/s10787-019-00582-9","journal-title":"Inflammopharmacology"},{"issue":"575\u201397","key":"870_CR39","doi-asserted-by":"publisher","first-page":"v","DOI":"10.1016\/j.cveq.2005.08.004","volume":"21","author":"TN Trumble","year":"2005","unstructured":"Trumble TN (2005) The use of nutraceuticals for osteoarthritis in horses. Vet Clin North Am Equine Pract 21(575\u201397):v\u2013vi. https:\/\/doi.org\/10.1016\/j.cveq.2005.08.004","journal-title":"Vet Clin North Am Equine Pract"},{"key":"870_CR40","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1016\/j.joca.2016.02.005","volume":"24","author":"M Udo","year":"2016","unstructured":"Udo M, Muneta T, Tsuji K, Ozeki N, Nakagawa Y, Ohara T, Saito R, Yanagisawa K, Koga H, Sekiya I (2016) Monoiodoacetic acid induces arthritis and synovitis in rats in a dose- and time-dependent manner: proposed model-specific scoring systems. Osteoarthr Cartil 24:1284\u20131291. https:\/\/doi.org\/10.1016\/j.joca.2016.02.005","journal-title":"Osteoarthr Cartil"},{"key":"870_CR41","doi-asserted-by":"publisher","DOI":"10.4238\/gmr.15027963","author":"J Wang","year":"2016","unstructured":"Wang J, Wang G, Sun GW (2016) Role of PPAR\u03b1 in down-regulating AGE-induced TGF-\u03b2 and MMP-9 expressions in chondrocytes. Genet Mol Res. https:\/\/doi.org\/10.4238\/gmr.15027963","journal-title":"Genet Mol Res"},{"key":"870_CR42","doi-asserted-by":"publisher","first-page":"15040","DOI":"10.1038\/boneres.2015.40","volume":"4","author":"W Zhang","year":"2016","unstructured":"Zhang W, Ouyang H, Dass CR, Xu J (2016) Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res 4:15040. https:\/\/doi.org\/10.1038\/boneres.2015.40","journal-title":"Bone Res"}],"container-title":["Inflammopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-021-00870-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10787-021-00870-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10787-021-00870-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T22:21:42Z","timestamp":1634163702000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10787-021-00870-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,1]]},"references-count":42,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,10]]}},"alternative-id":["870"],"URL":"https:\/\/doi.org\/10.1007\/s10787-021-00870-3","relation":{},"ISSN":["0925-4692","1568-5608"],"issn-type":[{"value":"0925-4692","type":"print"},{"value":"1568-5608","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,1]]},"assertion":[{"value":"15 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 September 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All experiments using animals reported herein were performed according to protocols approved by the Institutional Animal Care and Use Committee of Hallym University (HallymR1 2018-75).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}