Department of Mechanical Engineering and Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA.
Biochem Biophys Res Commun. 2010 Oct 8;401(1):20-5. doi: 10.1016/j.bbrc.2010.08.135. Epub 2010 Sep 9.
Bone morphogenetic proteins (BMPs) play a dual role as a factor in both bone and cartilage development and correspondingly have the therapeutic potential to regenerate both tissues. Given this dual nature, previous in vitro research using BMPs has relied on distinct media formulations and culture conditions to drive undifferentiated cells to the osteogenic or chondrogenic lineage. To isolate the impact of culture conditions and to explore the effect of BMP-6 on murine adipose-derived mesenchymal cells (ASCs), ASCs were seeded in either monolayer or pellets in an identical medium containing BMP-6. Results indicate that BMP-6 differentially promotes osteogenesis and chondrogenesis in ASCs depending on culture conditions. BMP-6 potently induced alkaline phosphatase activity and mineralization in ASCs cultured in monolayer conditions. In contrast, BMP-6 enhanced proteoglycan accumulation in ASCs seeded in chondrogenic pellet culture. A comparison of gene expression suggests that the differentiating effect of BMP-6 is specific to the particular culture condition. This study highlights the importance of the interactions between chemical signaling and microenvironmental cues in directing cell fate.
骨形态发生蛋白（BMPs）在骨骼和软骨发育中均具有双重作用，因此具有再生这两种组织的治疗潜力。鉴于这种双重特性，先前使用 BMPs 的体外研究依赖于不同的培养基配方和培养条件，以促使未分化细胞向成骨或成软骨谱系分化。为了分离培养条件的影响，并探索 BMP-6 对小鼠脂肪间充质细胞（ASCs）的作用，将 ASCs 单层或微载体接种于含有 BMP-6 的相同培养基中。结果表明，BMP-6 根据培养条件的不同，对 ASCs 的成骨和成软骨分化具有不同的促进作用。BMP-6 在单层培养条件下强烈诱导 ASCs 的碱性磷酸酶活性和矿化。相比之下，BMP-6 增强了在软骨形成微载体培养中接种的 ASCs 的蛋白聚糖积累。基因表达的比较表明，BMP-6 的分化作用特定于特定的培养条件。这项研究强调了化学信号和微环境线索之间相互作用在指导细胞命运中的重要性。
