TY - JOUR AU - Li, Ziru AU - Hardij, Julie AU - Evers, Simon S. AU - Hutch, Chelsea R. AU - Choi, Sarah M. AU - Shao, Yikai AU - Learman, Brian S. AU - Lewis, Kenneth T. AU - Schill, Rebecca L. AU - Mori, Hiroyuki AU - Bagchi, Devika P. AU - Romanelli, Steven M. AU - Kim, Ki-Suk AU - Bowers, Emily AU - Griffin, Cameron AU - Seeley, Randy J. AU - Singer, Kanakadurga AU - Sandoval, Darleen A. AU - Rosen, Clifford J. AU - MacDougald, Ormond A. T1 - G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche PY - 2019/06/03/ AB - Bariatric surgeries are integral to the management of obesity and its metabolic complications. However, these surgeries cause bone loss and increase fracture risk through poorly understood mechanisms. In a mouse model, vertical sleeve gastrectomy (VSG) caused trabecular and cortical bone loss that was independent of sex, body weight, and diet, and this loss was characterized by impaired osteoid mineralization and bone formation. VSG had a profound effect on the bone marrow niche, with rapid loss of marrow adipose tissue, and expansion of myeloid cellularity, leading to increased circulating neutrophils. Following VSG, circulating granulocyte–colony stimulating factor (G-CSF) was increased in mice, and was transiently elevated in a longitudinal study of humans. Elevation of G-CSF was found to recapitulate many effects of VSG on bone and the marrow niche. In addition to stimulatory effects of G-CSF on myelopoiesis, endogenous G-CSF suppressed development of marrow adipocytes and hindered accrual of peak cortical and trabecular bone. Effects of VSG on induction of neutrophils and depletion of marrow adiposity were reduced in mice deficient for G-CSF; however, bone mass was not influenced. Although not a primary mechanism for bone loss with VSG, G-CSF plays an intermediary role for effects of VSG on the bone marrow niche. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI126173 VL - 129 IS - 6 UR - https://doi.org/10.1172/JCI126173 SP - 2404 EP - 2416 PB - The American Society for Clinical Investigation ER -