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Currently there is no cure for OA, partly due to the large gaps in our understanding of its underlying molecular and cellular mechanisms. Macrophage migration inhibitory factor (MIF) is a procytokine that mediates pleiotropic inflammatory effects in inflammatory diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, data on the role of MIF in OA is limited with conflicting results. We undertook this study to investigate the role of MIF in OA by examining <jats:italic>MIF<\/jats:italic> genotype, mRNA expression, and protein levels in the Newfoundland Osteoarthritis Study.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>One hundred nineteen end-stage knee\/hip OA patients, 16 RA patients, and 113 healthy controls were included in the study. Two polymorphisms in the <jats:italic>MIF<\/jats:italic> gene, rs755622, and -794 CATT<jats:sub>5-8<\/jats:sub>, were genotyped using polymerase chain reaction\u2013restriction fragment length polymorphism (PCR-RFLP) and PCR followed by automated capillary electrophoresis, respectively. <jats:italic>MIF<\/jats:italic> mRNA levels in articular cartilage and subchondral bone were measured by quantitative polymerase chain reaction. Plasma concentrations of MIF, tumor necrosis factor-alpha (TNF-\u03b1), interleukin-6 (IL-6), and interleukin-1 beta (IL-1\u03b2) were measured by enzyme-linked immunosorbent assay.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>rs755622 and -794 CATT<jats:sub>5-8<\/jats:sub> genotypes were not associated with <jats:italic>MIF<\/jats:italic> mRNA or protein levels or OA (all <jats:italic>p<\/jats:italic>\u2009\u2265\u20090.19). <jats:italic>MIF<\/jats:italic> mRNA level in cartilage was lower in OA patients than in controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.028) and RA patients (<jats:italic>p<\/jats:italic>\u2009=\u20090.004), while the levels in bone were comparable between OA patients and controls (<jats:italic>p<\/jats:italic>\u2009=\u20090.165). MIF protein level in plasma was lower in OA patients than in controls (<jats:italic>p<\/jats:italic>\u2009=\u20093.01\u2009\u00d7\u200910<jats:sup>\u221210<\/jats:sup>), while the levels of TNF-\u03b1, IL-6 and IL-1\u03b2 in plasma were all significantly higher in OA patients than in controls (all <jats:italic>p<\/jats:italic>\u2009\u2264\u20090.0007). Multivariable logistic regression showed lower MIF and higher IL-1\u03b2 protein levels in plasma were independently associated with OA (OR per SD increase\u2009=\u20090.10 and 8.08; 95% CI\u2009=\u20090.04\u20130.19 and 4.42\u201316.82, respectively), but TNF-\u03b1 and IL-6 became non-significant.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Reduced <jats:italic>MIF<\/jats:italic> mRNA and protein expression in OA patients suggested MIF might have a protective role in OA and could serve as a biomarker to differentiate OA from other joint disorders.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-021-02442-w","type":"journal-article","created":{"date-parts":[[2021,2,21]],"date-time":"2021-02-21T01:24:54Z","timestamp":1613870694000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Macrophage migration inhibitory factor may play a protective role in osteoarthritis"],"prefix":"10.1186","volume":"23","author":[{"given":"Ming","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zikun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liujun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dake","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieying","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Furey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Proton","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghua","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangju","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,20]]},"reference":[{"issue":"6","key":"2442_CR1","doi-asserted-by":"publisher","first-page":"1697","DOI":"10.1002\/art.34453","volume":"64","author":"RF Loeser","year":"2012","unstructured":"Loeser RF, Goldring SR, Scanzello CR, Goldring MB. 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