比利时鲁汶大学Geert Carmeliet及其小组的最新研究阐明了脂质可及性通过SOX9决定了骨骼祖细胞的命运。相关论文于2020年2月26日在线发表在《自然》杂志上。
研究人员发现在骨愈合过程中阻断血管入侵比骨骼祖细胞的成骨分化更有利于软骨生成。意外的是，此过程是由细胞外脂质可及性降低导致的。当脂质稀缺时，骨骼祖细胞激活与Sox9启动子结合的叉头框O（FOXO）转录因子，并增加Sox9的表达。
除了启动软骨生成外，SOX9还通过抑制脂肪酸氧化来充当细胞代谢的调节剂，从而使细胞适应无血管生活。该研究结果发现脂质稀缺是软骨发生的重要决定因素，揭示了脂质缺乏时FOXO转录因子的作用，并确定了SOX9是关键的代谢介质。这些数据突出了营养微环境在骨骼细胞命运决定中的重要性。
据悉，软骨的无血管特性使其成为独特的组织，但是仍然不知营养供应缺乏是否以及如何调节软骨生成。
附：英文原文
Title: Lipid availability determines fate of skeletal progenitor cells via SOX9
Author: Nick van Gastel, Steve Stegen, Guy Eelen, Sandra Schoors, Aurlie Carlier, Veerle W. Danils, Ninib Baryawno, Dariusz Przybylski, Maarten Depypere, Pieter-Jan Stiers, Dennis Lambrechts, Riet Van Looveren, Sophie Torrekens, Azeem Sharda, Patrizia Agostinis, Diether Lambrechts, Frederik Maes, Johan V. Swinnen, Liesbet Geris, Hans Van Oosterwyck, Bernard Thienpont, Peter Carmeliet, David T. Scadden, Geert Carmeliet
Issue&Volume: 2020-02-26
Abstract: The avascular nature of cartilage makes it a unique tissue1,2,3,4, but whether and how the absence of nutrient supply regulates chondrogenesis remain unknown. Here we show that obstruction of vascular invasion during bone healing favours chondrogenic over osteogenic differentiation of skeletal progenitor cells. Unexpectedly, this process is driven by a decreased availability of extracellular lipids. When lipids are scarce, skeletal progenitors activate forkhead box O (FOXO) transcription factors, which bind to the Sox9 promoter and increase its expression. Besides initiating chondrogenesis, SOX9 acts as a regulator of cellular metabolism by suppressing oxidation of fatty acids, and thus adapts the cells to an avascular life. Our results define lipid scarcity as an important determinant of chondrogenic commitment, reveal a role for FOXO transcription factors during lipid starvation, and identify SOX9 as a critical metabolic mediator. These data highlight the importance of the nutritional microenvironment in the specification of skeletal cell fate.
DOI: 10.1038/s41586-020-2050-1
Source: https://www.nature.com/articles/s41586-020-2050-1
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
