Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair
Placental growth factor mediates mesenchymal cell development, cartilage turnover, and bone remodeling during fracture repair
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DOI：
10.1172/jci26772
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发表时间：
2006-05-01
影响因子：
15.9
通讯作者：
Carmeliet, G
中科院分区：
文献类型：
--
作者：
Maes, C;Coenegrachts, L;Carmeliet, G
目前治疗延迟愈合或骨不连的方法大多无效。以前的研究表明，VEGF同系物胎盘生长因子（PIGF）在疾病中的作用比在健康中更重要。因此，我们研究了PlGF在半稳定化骨折愈合模型中的作用。缺乏PlGF的小鼠骨折修复受损，其特征在于骨痂中大量软骨积聚，使人联想到延迟或不愈合的骨折。PlGF是骨折伤口早期炎症细胞募集和血管化所必需的。然而，有趣的是，PlGF在修复过程的后续阶段也发挥了作用。事实上，在体内和体外的研究结果表明，PlGF诱导间充质祖细胞的增殖和成骨分化，并通过特定的MMP刺激软骨更新。在这个过程的后期，PIGF是通过刺激破骨细胞分化来重塑新形成的骨所必需的。由于PlGF表达在整个骨修复过程中增加，并且所有涉及的重要细胞类型表达其受体VEGFR-1，因此本数据表明PlGF是介导和协调骨折修复的关键方面所需的。因此，PlGF可能为骨折修复提供潜在的治疗优势。
Current therapies for delayed- or nonunion bone fractures are stiff largely ineffective. Previous studies indicated that the VEGF homolog placental growth factor (PIGF) has a more significant role in disease than in health. Therefore we investigated the role of PlGF in a model of semistabilized bone fracture healing. Fracture repair in mice lacking PlGF was impaired and characterized by a massive accumulation of cartilage in the callus, reminiscent of delayed- or nonunion fractures. PlGF was required for the early recruitment of inflammatory cells and the vascularization of the fracture wound. Interestingly, however, PlGF also played a role in the subsequent stages of the repair process. Indeed in vivo and in vitro findings indicated that PlGF induced the proliferation and osteogenic differentiation of mesenchymal progenitors and stimulated cartilage turnover by particular MMPs. Later in the process, PIGF was required for the remodeling of the newly formed bone by stimulating osteoclast differentiation. As PIGF expression was increased throughout the process of bone repair and all the important cell types involved expressed its receptor VEGFR-1, the present data suggest that PlGF is required for mediating and coordinating the key aspects of fracture repair. Therefore PlGF may potentially offer therapeutic advantages for fracture repair.