{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:20:14Z","timestamp":1792192814922,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32273080"],"award-info":[{"award-number":["32273080"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Abnormal chondrocyte hypertrophy and apoptosis are critical pathological changes in the steroid\u2010induced osteonecrosis of the femoral head (SONFH). The development of SONFH has been strongly linked to the Wingless\/Integrated (Wnt) pathway. However, the role of secreted frizzled\u2010related protein 4 (SFRP4), an endogenous inhibitor of the Wnt pathway, in cartilage damage in SONFH remains unclear. In this study, we successfully induced SONFH in rats using methylprednisolone (MP), and subsequently separated and cultured primary rat chondrocytes for mechanism study. We observed that chondrocytes demonstrated significant hypertrophy and apoptosis in both in\u00a0vivo and in\u00a0vitro studies following MP treatment, accompanied by significant activation of the Wnt\/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and Wnt\/JNK pathways. Furthermore, cell transfection experiments were conducted using SFRP4 small interfering RNA (si\u2010SFRP4) or SFRP4 overexpression plasmid (OE\u2010SFRP4). Transfection with OE\u2010SFRP4 transfection mitigated MP\u2010induced chondrocyte hypertrophy and apoptosis, also resulting in downregulation of the Wnt\/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and Wnt\/JNK pathways. Conversely, transfection with si\u2010SFRP4 exacerbated these effects. In conclusion, SFRP4 attenuates MP\u2010induced chondrocyte hypertrophy and apoptosis associated with Wnt\/Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and Wnt\/JNK pathways, indicating that SFRP4 may hold therapeutic potential in the treatment of SONFH.\n                  <\/jats:p>","DOI":"10.1002\/cph4.70052","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T05:07:20Z","timestamp":1758085640000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>SFRP<\/scp>\n                    4 Regulates Chondrocyte Hypertrophy and Apoptosis via Wnt\/Ca\n                    <sup>2+<\/sup>\n                    and Wnt\/\n                    <scp>JNK<\/scp>\n                    Pathways in Steroid\u2010Induced Osteonecrosis of the Femoral 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