@article{84381c4de62b4f5cb4a4b75ac6ba077c,
title = "Bone-derived sclerostin and Wnt/β-catenin signaling regulate PDGFRα+ adipoprogenitor cell differentiation",
abstract = "The Wnt signaling antagonist, sclerostin, is a potent suppressor of bone acquisition that also mediates endocrine communication between bone and adipose. As a result, Sost−/− mice exhibit dramatic increases in bone formation but marked decreases in visceral and subcutaneous adipose that are secondary to alterations in lipid synthesis and utilization. While interrogating the mechanism by which sclerostin influences adipocyte metabolism, we observed paradoxical increases in the adipogenic potential and numbers of CD45−:Sca1+:PDGFRα+ adipoprogenitors in the stromal vascular compartment of fat pads isolated from male Sost−/− mice. Lineage tracing studies indicated that sclerostin deficiency blocks the differentiation of PDGFRα+ adipoprogenitors to mature adipocytes in association with increased Wnt/β-catenin signaling. Importantly, osteoblast/osteocyte-specific Sost gene deletion mirrors the accumulation of PDGFRα+ adipoprogenitors, reduction in fat mass, and improved glucose metabolism evident in Sost−/− mice. These data indicate that bone-derived sclerostin regulates multiple facets of adipocyte physiology ranging from progenitor cell commitment to anabolic metabolism.",
keywords = "PDGFRα, Wnt, adipoprogenitor, adipose, bone, sclerostin, β-catenin",
author = "Kim, {Soohyun P.} and Hao Da and Lei Wang and Taketo, {Makoto M.} and Mei Wan and Riddle, {Ryan C.}",
note = "Funding Information: We are grateful for the assistance of staff from the Johns Hopkins University School of Medicine, Division of Hematology, Flow Cytometry Core Facility. We thank Dr Dwight Bergles of The Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine for providing Pdgfra‐CreER mice and Dr Aris Economides of Regeneron for providing the Sost mice. This work was supported by a Merit Review Award from the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development (BX003724, RCR) and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (DK099134, RCR). T2 iCOIN Funding Information: We are grateful for the assistance of staff from the Johns Hopkins University School of Medicine, Division of Hematology, Flow Cytometry Core Facility. We thank Dr Dwight Bergles of The Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine for providing Pdgfra-CreERT2 mice and Dr Aris Economides of Regeneron for providing the SostiCOIN mice. This work was supported by a Merit Review Award from the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development (BX003724, RCR) and a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (DK099134, RCR). Publisher Copyright: {\textcopyright} 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.",
year = "2021",
month = nov,
doi = "10.1096/fj.202100691R",
language = "English (US)",
volume = "35",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "John Wiley & Sons Inc.",
number = "11",
}