{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:30:24Z","timestamp":1788874224512,"version":"build-2803163510"},"reference-count":67,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":59,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the natural science foundation of China","doi-asserted-by":"crossref","award":["82201748"],"award-info":[{"award-number":["82201748"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"shanghai sailing program","award":["21YF1459200"],"award-info":[{"award-number":["21YF1459200"]}]},{"DOI":"10.13039\/501100001809","name":"the natural science foundation of China","doi-asserted-by":"crossref","award":["82571824"],"award-info":[{"award-number":["82571824"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"the natural science foundation of China","doi-asserted-by":"crossref","award":["82571824"],"award-info":[{"award-number":["82571824"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,9]]},"abstract":"<jats:p>\n                    Modic type 1 and 2 changes (MC-1 and MC-2) are highly prevalent in individuals with chronic low back pain, yet the cellular and molecular mechanisms underlying vertebral endplate degeneration remain poorly defined. Here, we report that osteoclastogenesis is markedly elevated in MC-1 and MC-2 lesions compared with MC-3 lesions, suggesting an active role for osteoclasts in the early stages of degeneration. Using a lumbar spine instability (LSI) mouse model, we demonstrate enhanced osteoclast activity in degenerating endplates. RNA sequencing of mononuclear cells isolated from the endplate and adjacent subchondral bone identified\n                    <jats:italic>Gdf15<\/jats:italic>\n                    as a potential upstream regulator of this process. Conditional knockout of\n                    <jats:italic>Gdf15<\/jats:italic>\n                    in monocytes reduced osteoclast formation, aberrant CD31\n                    <jats:sup>hi<\/jats:sup>\n                    Emcn\n                    <jats:sup>hi<\/jats:sup>\n                    angiogenesis, and pain-associated neurogenesis, ultimately mitigating endplate degeneration and mechanical allodynia. Mechanistically, GDF15 promoted the fusion of preosteoclasts by modulating the expression of Rho family small GTPases. In a humanized GDF15 knockin mouse model, therapeutic neutralization of GDF15 led to a reduction in osteoclast burden, improved endplate structure, and attenuated pain behavior. Together, these findings uncover a previously unrecognized role for GDF15 in driving osteoclast-mediated endplate degeneration and highlight its potential as a therapeutic target for the treatment of endplate-related chronic low back pain.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.190598","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T17:00:39Z","timestamp":1762880439000},"source":"Crossref","is-referenced-by-count":2,"title":["GDF15 induces excessive activation of osteoclasts within the vertebral endplates leading to early endplate degeneration"],"prefix":"10.1172","volume":"11","author":[{"given":"Xiaoqun","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhui","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Shanghai 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