{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:00:28Z","timestamp":1788872428189,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,7,26]],"date-time":"2013-07-26T00:00:00Z","timestamp":1374796800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NIH","award":["R01-AR-046177"],"award-info":[{"award-number":["R01-AR-046177"]}]},{"name":"NIH","award":["AR-048372"],"award-info":[{"award-number":["AR-048372"]}]},{"name":"NIH\/National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program","award":["Z01-AR-041184"],"award-info":[{"award-number":["Z01-AR-041184"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To determine whether HLA\u2013B27 expression alters the response of bone marrow monocytes from HLA\u2013B27\/human \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010microglobulin\u2013transgenic (B27\u2010Tg) rats to tumor necrosis factor \u03b1 (TNF\u03b1) and, if so, whether this affects the cells involved in bone homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Bone marrow monocytes were treated with RANKL or with TNF\u03b1 to promote osteoclast formation. Osteoclasts were quantified by counting. Gene expression was measured using quantitative polymerase chain reaction analysis, and protein was detected by enzyme\u2010linked immunosorbent assay, immunoblotting, or immunofluorescence. Effects of endogenously produced cytokines on osteoclast formation were determined with neutralizing antibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TNF\u03b1 treatment enhanced osteoclast formation 2.5\u2010fold in HLA\u2013B27\u2013expressing cells as compared to wild\u2010type or to HLA\u2013B7\/human \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      \u2010microglobulin\u2013expressing monocytes. TNF\u03b1 induced \u223c4\u2010fold up\u2010regulation of HLA\u2013B27, which was associated with the accumulation of misfolded heavy chains, binding of the endoplasmic reticulum (ER) chaperone BiP, and activation of an ER stress response, which was not seen with HLA\u2013B7. No differences were seen with RANKL\u2010induced osteoclastogenesis. Enhanced interleukin\u20101\u03b1 (IL\u20101\u03b1) production from ER\u2010stressed bone marrow monocytes from B27\u2010Tg rats was found to be necessary and sufficient for enhanced osteoclast formation. However, bone marrow monocytes from B27\u2010Tg rats also produced more interferon\u2010\u03b2 (IFN\u03b2), which attenuated the effect of IL\u20101\u03b1 on osteoclast formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HLA\u2013B27\u2013induced ER stress alters the response of bone marrow monocytes from B27\u2010Tg rats to TNF\u03b1, which is associated with enhanced production of IL\u20101\u03b1 and IFN\u03b2, cytokines that exhibit opposing effects on osteoclast formation. The altered response of cells expressing HLA\u2013B27 to proinflammatory cytokines suggests that this class I major histocompatibility complex allele may contribute to the pathogenesis of spondyloarthritis and its unique phenotype through downstream effects involving alterations in bone homeostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.38001","type":"journal-article","created":{"date-parts":[[2013,5,10]],"date-time":"2013-05-10T15:26:05Z","timestamp":1368199565000},"page":"2123-2131","source":"Crossref","is-referenced-by-count":34,"title":["HLA\u2013B27 Alters the Response to Tumor Necrosis Factor \u03b1 and Promotes Osteoclastogenesis in Bone Marrow Monocytes From HLA\u2013B27\u2013Transgenic Rats"],"prefix":"10.1002","volume":"65","author":[{"given":"Gerlinde","family":"Layh\u2010Schmitt","sequence":"first","affiliation":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH Bethesda 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