{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:26:10Z","timestamp":1791919570551,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to determine whether alignment correction by high tibial osteotomy (HTO) can change the biologic intraarticular microenvironment of osteoarthritic (OA) knees.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Synovial tissue (ST) and fluid (SF) were collected from the affected knees of 31 OA patients during initial HTO and plate removal surgeries. Changes in gene expression in ST were investigated by microarray and real\u2010time polymerase chain reaction (PCR). ST specimens were also evaluated histologically using synovitis scores and immunofluorescence staining to determine macrophage polarity. Cytokines and chemokines in SF were analyzed by enzyme\u2010linked immunosorbent assays. The mechanism of macrophage polarization was investigated in human peripheral blood mononuclear cell\u2013derived macrophages and fibroblast\u2010like synoviocytes (FLS) stimulated with cartilage fragments. We also evaluated Spearman correlations between Knee Injury and Osteoarthritis Outcome scores (KOOS) and macrophage\u2010related gene expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The microarray results indicated down\u2010regulated inflammatory genes and pathways. Real\u2010time PCR determined that genes expressing proinflammatory\n                      <jats:italic>IL1B<\/jats:italic>\n                      and\n                      <jats:italic>IL6<\/jats:italic>\n                      were down\u2010regulated and M2 macrophage\u2013related\n                      <jats:italic>IL1RA<\/jats:italic>\n                      ,\n                      <jats:italic>IL10<\/jats:italic>\n                      ,\n                      <jats:italic>CCL18<\/jats:italic>\n                      , and\n                      <jats:italic>CD206<\/jats:italic>\n                      were up\u2010regulated. Histologic findings revealed attenuated synovitis scores and a shift from M1 to M2 macrophages. Interleukin\u20101\u03b2 (IL\u20101\u03b2) concentrations in SF decreased after HTO. Cartilage fragments were responsible for M1 macrophage polarization and proinflammatory gene and protein expression in macrophages, whereas cartilage fragments up\u2010regulated only IL\u20106 protein in FLS. Postoperative KOOS positively correlated with the expression of the M2\u2010related genes\n                      <jats:italic>CCL18<\/jats:italic>\n                      and\n                      <jats:italic>CD206<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Correction of lower limb alignment with HTO attenuated synovial inflammation and changed macrophage polarization from M1 to M2, suggesting an improved intraarticular environment in knee OA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.42424","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T02:50:36Z","timestamp":1671418236000},"page":"950-960","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Knee Alignment Correction by High Tibial Osteotomy Reduces Symptoms and Synovial Inflammation in Knee Osteoarthritis Accompanied by Macrophage Phenotypic Change From\n                    <scp>M1<\/scp>\n                    to\n                    <scp>M2<\/scp>"],"prefix":"10.1002","volume":"75","author":[{"given":"Shigeo","family":"Yoshida","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-3826","authenticated-orcid":false,"given":"Kohei","family":"Nishitani","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Yoshitomi","sequence":"additional","affiliation":[{"name":"Department of Immunology, Graduate School of Medicine Kyoto University  Kyoto 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