{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:40:05Z","timestamp":1787067605418,"version":"build-2736575974"},"reference-count":60,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"758","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:p>\n                    Proinflammatory cytokines play critical roles in the pathogenesis of joint diseases. Using a mass spectrometry\u2013based cloning approach, we identified Semaphorin 4D (Sema4D) as an inflammatory cytokine that directly promoted cartilage destruction.\n                    <jats:italic>Sema4d<\/jats:italic>\n                    -deficient mice showed less cartilage destruction than wild-type mice in a model of rheumatoid arthritis. Sema4D induced a proinflammatory response in mouse articular chondrocytes characterized by the induction of proteolytic enzymes that degrade cartilage, such as matrix metalloproteinases (MMPs) and aggrecanases. The activation of\n                    <jats:italic>Mmp13<\/jats:italic>\n                    and\n                    <jats:italic>Mmp3<\/jats:italic>\n                    expression in articular chondrocytes by Sema4D did not depend on RhoA, a GTPase that mediates Sema4D-induced cytoskeletal rearrangements. Instead, it required NF-\u03baB signaling and Ras-MEK-Erk1\/2 signaling downstream of the receptors Plexin-B2 and c-Met and depended on the transcription factors I\u03baB\u03b6 and C\/EBP\u03b4. Genetic and pharmacological blockade of these Sema4D signaling pathways inhibited MMP induction in chondrocytes and cartilage destruction in femoral head organ culture. Our results reveal a mechanism by which Sema4D signaling promotes cartilage destruction.\n                  <\/jats:p>","DOI":"10.1126\/scisignal.abl5304","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T13:58:12Z","timestamp":1667311092000},"source":"Crossref","is-referenced-by-count":15,"title":["Semaphorin 4D induces articular cartilage destruction and inflammation in joints by transcriptionally reprogramming chondrocytes"],"prefix":"10.1126","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5021-5494","authenticated-orcid":true,"given":"Tomohiko","family":"Murakami","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biochemistry, Osaka University Graduate School of Dentistry, Osaka 565-0871, 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