抗硬骨素或 G-CSF 受体抗体分别部分消除了垂直袖状胃切除术后的骨或骨髓脂肪细胞丢失。

Antibodies to sclerostin or G-CSF receptor partially eliminate bone or marrow adipocyte loss, respectively, following vertical sleeve gastrectomy.

机构信息

University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, United States of America; MaineHealth Institute for Research, Scarborough, ME, United States of America.

University of Michigan Medical School, Department of Molecular & Integrative Physiology, Ann Arbor, MI, United States of America.

出版信息

Bone. 2023 Apr;169:116682. doi: 10.1016/j.bone.2023.116682. Epub 2023 Jan 26.

Abstract

Vertical sleeve gastrectomy (VSG), the most utilized bariatric procedure in clinical practice, greatly reduces body weight and improves a variety of metabolic disorders. However, one of its long-term complications is bone loss and increased risk of fracture. Elevated circulating sclerostin (SOST) and granulocyte-colony stimulating factor (G-CSF) concentrations have been considered as potential contributors to VSG-associated bone loss. To test these possibilities, we administrated antibodies to SOST or G-CSF receptor and investigated alterations to bone and marrow niche following VSG. Neutralizing either SOST or G-CSF receptor did not alter beneficial effects of VSG on adiposity and hepatic steatosis, and anti-SOST treatment provided a further improvement to glucose tolerance. SOST antibodies partially reduced trabecular and cortical bone loss following VSG by increasing bone formation, whereas G-CSF receptor antibodies had no effects on bone mass. The expansion in myeloid cellularity and reductions in bone marrow adiposity seen with VSG were partially eliminated by treatment with Anti-G-CSF receptor. Taken together, these experiments demonstrate that antibodies to SOST or G-CSF receptor may act through independent mechanisms to partially block effects of VSG on bone loss or marrow niche cells, respectively.

摘要

胃袖状切除术(VSG)是临床实践中应用最广泛的减肥手术,它可以显著减轻体重并改善多种代谢紊乱。然而,其长期并发症之一是骨丢失和骨折风险增加。循环中骨硬化素(SOST)和粒细胞集落刺激因子(G-CSF)浓度升高被认为是 VSG 相关骨丢失的潜在原因。为了验证这些可能性,我们给予了 SOST 或 G-CSF 受体的抗体,并研究了 VSG 后骨和骨髓龛的变化。中和 SOST 或 G-CSF 受体都不会改变 VSG 对肥胖和肝脂肪变性的有益作用,而抗 SOST 治疗进一步改善了葡萄糖耐量。SOST 抗体通过增加骨形成部分减少了 VSG 后的小梁和皮质骨丢失,而 G-CSF 受体抗体对骨量没有影响。VSG 引起的髓样细胞数量增加和骨髓脂肪减少部分被抗 G-CSF 受体治疗消除。总之,这些实验表明,SOST 或 G-CSF 受体的抗体可能通过独立的机制分别部分阻断 VSG 对骨丢失或骨髓龛细胞的作用。

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