{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:56:13Z","timestamp":1790708173025,"version":"4.1.0"},"reference-count":88,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Bone marrow edema (BME), a common magnetic resonance imaging (MRI) finding characterized by increased fluid signal, is associated with pain and structural deterioration in conditions such as osteoarthritis and avascular necrosis. The pathophysiology of BME involves a complex interplay of vascular leakage, inflammation, microdamage, disrupted bone remodeling, and increased marrow adiposity. Sirtuin 1 (SIRT1), an NAD\n                      <jats:sup>+<\/jats:sup>\n                      \u2010dependent deacetylase, is a critical regulator of bone homeostasis, promoting osteoblastogenesis, inhibiting osteoclastogenesis, and suppressing bone marrow adipose tissue (BMAT) formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This review synthesizes existing experimental, preclinical, and clinical evidence concerning SIRT1 in bone homeostasis and examines its potential relationship with mechanisms implicated in BME. Particular attention is given to endothelial integrity, inflammatory signaling, oxidative stress, bone remodeling, BMAT, and mesenchymal stem cell fate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Current evidence supports a biologically plausible role for SIRT1 dysfunction in the development and persistence of BME. Reduced SIRT1 activity may contribute to vascular permeability, prolonged inflammatory signaling, oxidative stress, impaired osteoblastogenesis, enhanced osteoclastogenesis, and increased marrow adiposity. Although direct evidence linking SIRT1 specifically to BME remains limited, converging indirect evidence suggests that SIRT1 activation could mitigate several core drivers of edema. SIRT1 activators, including resveratrol and NAD\n                      <jats:sup>+<\/jats:sup>\n                      precursors, therefore have potential therapeutic relevance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>SIRT1 may represent a mechanistic interface between BME, inflammation, vascular dysfunction, and disturbed bone remodeling. Combination strategies targeting SIRT1 together with vascular leakage and inflammation may offer additional therapeutic potential. However, direct lesion\u2010level and clinical evidence is required to establish causality, define therapeutic efficacy, and validate SIRT1 as a target for preventing or resolving BME.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/iid3.70505","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:07:39Z","timestamp":1790165259000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of SIRT1 in Mediating Bone Marrow Edema and Its Interface With Bone Remodeling"],"prefix":"10.1002","volume":"14","author":[{"given":"Yiming","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Orthopaedics (Joint and Sports Medicine) Chongqing Traditional Chinese Medicine Hospital (Nanqiaosi Campus) Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Li","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongji","family":"Zheng","sequence":"additional","affiliation":[{"name":"Joint Ward 2 Traditional Chinese Medicine Hospital Tongliang Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3258-7987","authenticated-orcid":false,"given":"Yuanyi","family":"Tang","sequence":"additional","affiliation":[{"name":"Joint Ward 2 Traditional Chinese Medicine Hospital Tongliang Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-024-00752-w"},{"key":"e_1_2_12_3_1","unstructured":"J. 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