近日，美国华盛顿大学医学院Steven L. Teitelbaum团队发现，成年小鼠脂肪细胞的消除能够诱导大量的骨增加。这一研究成果于2020年10月6日在线发表在国际学术期刊《细胞—代谢》上。

为了探究产后脂肪细胞消除对骨细胞的影响，研究人员将表达可诱导的灵长类白喉毒素受体（DTR）的小鼠与带有脂联素（ADQ）-Cre的小鼠进行交配。 DTR激活消除了这些DTR^ADQ小鼠的外周和骨髓脂肪细胞。在DTR激活的4天之内，由于刺激了成骨作用，DTR^ADQ小鼠的全身骨量开始增加，在DTR治疗后的10–14天膨胀了1,000％。

这种脂肪细胞敲除介导的骨骼质量增强反映出消除了其抑制剂后骨形态发生蛋白（BMP）受体的激活，这与同时的表皮生长因子（EGF）受体信号传导有关。DTR^ADQ诱导的骨硬化不是由于周围脂肪细胞的消除引起的，而是可能表达ADQ的骨髓脂肪细胞的消除。因此，靶向BMP受体抑制剂（具有短期EGF受体活化作用）的合成代谢药物可能是大幅增加骨骼质量以预防或逆转病理性骨丢失的一种手段。

Title: Ablation of Fat Cells in Adult Mice Induces Massive Bone Gain

Author: Wei Zou, Nidhi Rohatgi, Jonathan R. Brestoff, Yongjia Li, Ruteja A. Barve, Eric Tycksen, Yung Kim, Matthew J. Silva, Steven L. Teitelbaum

Issue&Volume: 2020-10-06

Abstract: Adipocytes control bone mass, but the mechanism is unclear. To explore the effectof postnatal adipocyte elimination on bone cells, we mated mice expressing an inducibleprimate diphtheria toxin receptor (DTR) to those bearing adiponectin (ADQ)-Cre. DTRactivation 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 by10–14 days post-DTR treatment. This adipocyte ablation-mediated enhancement of skeletalmass reflected bone morphogenetic protein (BMP) receptor activation following theelimination of its inhibitors, associated with simultaneous epidermal growth factor(EGF) receptor signaling. DTRADQ-induced osteosclerosis is not due to ablation of peripheral adipocytes but likelyreflects the elimination of marrow ADQ-expressing cells. Thus, anabolic drugs targetingBMP receptor inhibitors with short-term EGF receptor activation may be a means ofprofoundly increasing skeletal mass to prevent or reverse pathological bone loss.

DOI: 10.1016/j.cmet.2020.09.011

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30489-7