@article{cff88a86c08040e88a5ffa80f909e852,
title = "Ablation of Fat Cells in Adult Mice Induces Massive Bone Gain",
abstract = "Adipocytes control bone mass, but the mechanism is unclear. To explore the effect of postnatal adipocyte elimination on bone cells, we mated mice expressing an inducible primate diphtheria toxin receptor (DTR) to those bearing adiponectin (ADQ)-Cre. DTR activation eliminates peripheral and marrow adipocytes in these DTRADQ mice. Within 4 days of DTR activation, the systemic bone mass of DTRADQ mice began to increase due to stimulated osteogenesis, with a 1,000% expansion by 10–14 days post-DTR treatment. This adipocyte ablation-mediated enhancement of skeletal mass reflected bone morphogenetic protein (BMP) receptor activation following the elimination of its inhibitors, associated with simultaneous epidermal growth factor (EGF) receptor signaling. DTRADQ-induced osteosclerosis is not due to ablation of peripheral adipocytes but likely reflects the elimination of marrow ADQ-expressing cells. Thus, anabolic drugs targeting BMP receptor inhibitors with short-term EGF receptor activation may be a means of profoundly increasing skeletal mass to prevent or reverse pathological bone loss.",
keywords = "BMPR activation, adipocyte, bone formation, heparin-binding epidermal like growth factor",
author = "Wei Zou and Nidhi Rohatgi and Brestoff, {Jonathan R.} and Yongjia Li and Barve, {Ruteja A.} and Eric Tycksen and Yung Kim and Silva, {Matthew J.} and Teitelbaum, {Steven L.}",
note = "Funding Information: This research was supported by the following grants from the National Institutes of Health: R01 AR047867 (M.J.S.), P30 AR074992 (M.J.S. and S.L.T.), R37 AR046523 (S.L.T.), and R01 DK111389 (S.L.T.). J.R.B. was supported by the NIH Office of the Director (DP5 OD028125), Burroughs Wellcome Fund (CAMS 1019648), and Children's Discovery Institute (MI-F-2019-795). We thank Heather Zannit, PhD, for providing 3.6Col1-tk breeders, and Michael Brodt of the WU Musculoskeletal Structure and Strength Core for supporting ?CT and mechanical testing. W.Z. designed and performed experiments, analyzed all data, and wrote the manuscript. N.R. J.R.B. Y.L. and Y.K. performed experiments; R.A.B. and E.T. analyzed the RNA-seq data; and M.J.S. and S.L.T. designed experiments and wrote the manuscript. R.A.B. may receive royalty income based on the CompBio technology developed by R.A.B. and licensed by Washington University to PercayAI. All other authors declare no competing interests. Funding Information: This research was supported by the following grants from the National Institutes of Health : R01 AR047867 (M.J.S.), P30 AR074992 (M.J.S. and S.L.T.), R37 AR046523 (S.L.T.), and R01 DK111389 (S.L.T.). J.R.B. was supported by the NIH Office of the Director ( DP5 OD028125 ), Burroughs Wellcome Fund (CAMS 1019648 ), and Children{\textquoteright}s Discovery Institute ( MI-F-2019-795 ). We thank Heather Zannit, PhD, for providing 3.6Col1-tk breeders, and Michael Brodt of the WU Musculoskeletal Structure and Strength Core for supporting μCT and mechanical testing. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = nov,
day = "3",
doi = "10.1016/j.cmet.2020.09.011",
language = "English",
volume = "32",
pages = "801--813.e6",
journal = "Cell Metabolism",
issn = "1550-4131",
number = "5",
}