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G-CSF partially mediates effects of sleeve gastrectomy on the bone marrow niche.
Authors Li Z, Hardij J, Evers SS, Hutch CR, Choi SM, Shao Y, Learman BS, Lewis KT,
Schill RL, Mori H, Bagchi DP, Romanelli SM, Kim KS, Bowers E, Griffin C, Seeley
RJ, Singer K, Sandoval DA, Rosen CJ, MacDougald OA
Submitted By Submitted Externally on 6/24/2019
Status Published
Journal The Journal of clinical investigation
Year 2019
Date Published 5/1/2019
Volume : Pages 130 : 2404 - 2416
PubMed Reference 31063988
Abstract 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


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