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As dysbiosis may serve as a common contributor, the anti-microbial pleiotropic factor lipocalin 2 could be a potential mediator due to its roles in inflammation and bone homeostasis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Baseline colonic pathology was conducted in the <jats:italic>ank\/ank<\/jats:italic> mouse model. Serum lipocalin 2 was analyzed by ELISA, in <jats:italic>ank\/ank<\/jats:italic> mutants versus C3FeB6-A\/A<jats:sup>w-j<\/jats:sup><jats:italic>wt\/wt<\/jats:italic>, in patients with concurrent AS-IBD, AS alone, IBD alone, or mechanical back pain, and in healthy controls. In the <jats:italic>ank\/ank<\/jats:italic> mouse model, the expression of nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR\u03b3) was examined by real-time PCR. Intraperitoneal injection was done with the PPAR\u03b3 agonist rosiglitazone or antagonist bisphenol A diglycidyl ether for four consecutive days. Serum levels of lipocalin 2 were examined on the sixth day.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>This study showed that the <jats:italic>ank\/ank<\/jats:italic> mice with fully fused spines had concurrent colonic inflammation. By first using the <jats:italic>ank\/ank<\/jats:italic> mouse model with progressive ankylosis and subclinical colonic inflammation, confirmed in patients with concurrent AS and IBD, elevated circulating lipocalin 2 levels were associated with the coexisting ankylosis and gut inflammation. The intracellular pathway of lipocalin 2 was further investigated with the <jats:italic>ank\/ank<\/jats:italic> mouse model involving PPAR\u03b3. Colonic expression of PPAR\u03b3 was negatively associated with the degree of gut inflammation. The PPAR\u03b3 agonist rosiglitazone treatment significantly upregulated the serum levels of lipocalin 2, suggesting a potential regulatory role of PPAR\u03b3 in the aberrant expression of lipocalin 2.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In summary, lipocalin 2 modulated by PPAR\u03b3 could be a potential pathway involved in concurrent inflammation and ankylosis in AS and IBD.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13075-020-02149-4","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T14:02:46Z","timestamp":1584540166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Lipocalin 2 links inflammation and ankylosis in the clinical overlap of inflammatory bowel disease (IBD) and ankylosing spondylitis (AS)"],"prefix":"10.1186","volume":"22","author":[{"given":"Aifeng","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Inman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J.","family":"Streutker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenbo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth P. 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