Differential temporal expression of members of the transforming growth factor β superfamily during murine fracture healing
Differential temporal expression of members of the transforming growth factor β superfamily during murine fracture healing
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DOI：
10.1359/jbmr.2002.17.3.513
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发表时间：
2002-03-01
影响因子：
6.2
通讯作者：
Einhorn, TA
中科院分区：
文献类型：
--
作者：
Cho, TJ;Gerstenfeld, LC;Einhorn, TA
骨折愈合是一个独特的出生后修复过程，其中软骨内和膜内骨形成的事件遵循一个可定义的时间顺序。在小鼠胫骨骨折愈合的28天内，研究了转化生长因子β（TGF-β）超家族成员信使RNA（mRNA）表达的时间模式。骨形态发生蛋白2（BMP-2）和生长分化因子8（GDF 8）在骨折后第1天表达最高，表明它们在愈合事件级联中作为早期反应基因的作用。鉴于其作为骨骼肌生长的负调节剂的已知作用，GDF 8至第1天的限制性表达表明其可以类似地在骨折愈合过程的早期调节细胞分化。GDF 5、TGF-β 2和TGF-β 3在第7天显示最大表达，此时II型胶原蛋白表达在软骨形成期间达到峰值。相反，BMP-3，BMP-4，BMP-7，和BMP-8表现出从第14天到第21天，当钙化软骨的再吸收和成骨细胞募集最活跃的表达的限制期。TGF-β 1、BMP-5和BMP-6以及GDF 10从第3天至第21天组成型表达。然而，在同一时间段内，GDF 3、GDF 6和GDF 9不能被检测到，GDF 1以极低的水平表达。这些发现表明，TGF-β超家族的几个成员积极参与骨折愈合，虽然它们在结构和功能上密切相关，但每个成员都有不同的时间表达模式，并在骨折愈合中发挥潜在的独特作用。
Fracture healing is a unique postnatal repair process in which the events of endochondral and intramembranous bone formation follow a definable temporal sequence. The temporal patterns of messenger RNA (mRNA) expression for members of the transforming growth factor beta (TGF-beta) superfamily were examined over a 28-day period of fracture healing in mouse tibias. Bone morphogenetic protein 2 (BMP-2) and growth and differentiation factor 8 (GDF8) showed maximal expression on day 1 after fracture, suggesting their roles as early response genes in the cascade of healing events. Restricted expression of GDF8 to day 1, in light of its known actions as a negative regulator of skeletal muscle growth, suggests that it may similarly regulate cell differentiation early in the fracture healing process. GDF5, TGF-beta2, and TGF-beta3 showed maximal expression on day 7, when type II collagen expression peaked during cartilage formation. In contrast, BMP-3, BMP-4, BMP-7, and BMP-8 showed a restricted period of expression from day 14 through day 21, when the resorption of calcified cartilage and osteoblastic recruitment were most active. TGF-beta1, BMP-5 and BMP-6, and GDF10 were constitutively expressed from day 3 to day 21. However, during the same time period, GDF3, GDF6, and GDF9 could not be detected, and GDF1 was expressed at extremely low levels. These findings suggest that several members of the TGF-beta superfamily are actively involved in fracture healing and although they are closely related both structurally and functionally, each has a distinct temporal expression pattern and potentially unique role in fracture healing.