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Here, plasma ELISA analysis showed preferential elevation of circulating C-type lectin domain family 3 member B (CLEC3B) in the high-BMI PMOP subgroup. CLEC3B was enriched in adipose tissue and negatively regulated by estradiol.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , adipose-targeted overexpression of\n                    <jats:italic>Clec3b<\/jats:italic>\n                    increased trabecular bone mass and promoted osteoblast-associated bone formation without markedly altering osteoclast-related parameters. To investigate the underlying mode of action, we used an adipocyte\u2013osteoblast conditioned-medium model. Conditioned medium from\n                    <jats:italic>Clec3b<\/jats:italic>\n                    -overexpressing adipocytes promoted osteogenic differentiation of primary calvarial osteoblasts, whereas conditioned medium from\n                    <jats:italic>Clec3b<\/jats:italic>\n                    -silenced adipocytes produced the opposite effect. Adipocyte transcriptomic analysis nominated Igfbp4 as a secretome-associated candidate reduced after\n                    <jats:italic>Clec3b<\/jats:italic>\n                    overexpression. Recombinant insulin-like growth factor-binding protein 4 (IGFBP4) reduced the increases in osteogenic gene expression, RUNX2 abundance, and matrix deposition induced by\n                    <jats:italic>Clec3b<\/jats:italic>\n                    -enriched conditioned medium. In parallel, recombinant IGFBP4 (rIGFBP4) partially attenuated the associated changes in mitochondrial superoxide-related fluorescence, intracellular oxidative fluorescence, mitochondrial membrane potential, and PINK1\/PRKN-related signaling. Collectively, the data are consistent with a model whereby adipose-derived CLEC3B promotes osteogenesis through a CLEC3B\u2013IGFBP4-related paracrine axis associated with mitochondrial adaptation in osteoblasts. These findings define a testable adipose-to-bone signaling mechanism relevant to osteoblast dysfunction in PMOP.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>\n                  <jats:p>Proposed adipose-to-bone CLEC3B\u2013IGFBP4-related paracrine axis associated with mitochondrial adaptation in osteoblasts.<\/jats:p>\n                  <jats:p>\u2022 Plasma CLEC3B is preferentially elevated in high-BMI PMOP.<\/jats:p>\n                  <jats:p>\n                    \u2022 Adipose-targeted\n                    <jats:italic>Clec3b<\/jats:italic>\n                    overexpression promotes trabecular bone accrual.\n                  <\/jats:p>\n                  <jats:p>\n                    \u2022 Adipocytic\n                    <jats:italic>Clec3b<\/jats:italic>\n                    overexpression suppresses IGFBP4 and enhances osteogenic differentiation.\n                  <\/jats:p>\n                  <jats:p>\u2022 The CLEC3B\u2013IGFBP4-related axis is associated with mitochondrial adaptation in osteoblasts.<\/jats:p>","DOI":"10.1007\/s10565-026-10223-x","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:48:09Z","timestamp":1783086489000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipose-derived CLEC3B promotes osteogenesis through a CLEC3B\u2013IGFBP4-related paracrine axis associated with mitochondrial adaptation in postmenopausal osteoporosis"],"prefix":"10.1007","volume":"42","author":[{"given":"Zhihao","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangliang","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaobo","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoyang","family":"Zong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxing","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3020-8139","authenticated-orcid":false,"given":"Dageng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"10223_CR1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/s1043-2760(00)00301-5","volume":"11","author":"RS Ahima","year":"2000","unstructured":"Ahima RS, Flier JS. 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