GDF REGULATION OF ENDOCHONDRAL BONE GROWTH

描述（取自应用程序）： 近年来，人们在理解 生长板内软骨细胞成熟的分子调控， 生长因子的产生及其受体的调节， 受体介导的跨膜信号传导过程。生长/分化 TGF-β因子（GDF）代表TGF-β家族的一个独特的子集， 在调节软骨内骨生长中起作用。GDF的证据 参与主要来自于GDF-5/CCRs-1的突变， Hunter-Thompson肢端中肢软骨发育不良的个体， GDF-5缺乏的长骨长度减少 短足症小鼠考虑到GDF-5/CCR 1 -1与软骨发育不良之间的联系， 在人类中，其他软骨发育不良疾病可能与 相关GDF/CCLs家族成员的突变。这项研究的目的是 通过研究GDF 5、6和7对软骨内骨生长的影响， 缺乏这些信号肽的动物。我们会检查老鼠 编码GDF 5、6或7的基因发生突变。每一个基因， 有趣的是，将研究三组10只健康雄性小鼠，代表 4周龄时的突变型（-/-）和杂合型（+/-）对照同窝仔。 使用体视学和软骨细胞动力学的经典方法， 从胫骨近端肱骨近端和第四根肋骨 检查以检验GDF 5、6或7缺陷的小鼠将 表现出软骨内骨生长受损。拟议的详细分析 体视学和软骨细胞动力学参数将有助于精确识别 哪些生长板细胞群受GDF 5，6， 7.未来的研究将把这些调查扩展到两倍和三倍的GDF 家族成员突变，以及其他 在各种单，双， 三重GDF突变

DESCRIPTION (Taken from the application): In recent years, numerous advances have been made towards understanding the molecular regulation of chondrocyte maturation within the growth plate through the production of growth factors and the regulation of their receptors and receptor-mediated transmembrane signaling processes. The growth/differentiation factors (GDFs) represent a distinct subset of the TGF-beta family which may play a role in regulating endochondral bone growth. Evidence for GDF involvement comes largely from the documented mutation in GDF-5/CDMP-1 in individuals with acromesomelic chondrodysplasia of the Hunter-Thompson and Grebe types, and a reduction in the length of the long bones of GDF-5 deficient brachypodism mice. Given the link between GDF-5/CDMP-1 and chondrodysplasia in humans, it is likely that other chondrodysplastic disorders are linked to mutations in related GDF/CDMP family members. The goal of this research is to examine the effect of GDFs 5, 6, & 7 on endochondral bone growth by studying animals with a deficiency in these signaling peptides. We will examine mice with mutations in the genes which code for GDF 5, 6 or 7. For each gene of interest, three groups of ten healthy male mice will be studied, representing mutant (-/-) and heterozygous (+/-) control littermates at 4 weeks of age. Using classical methods of stereology and chondrocyte kinetics, growth plates from the proximal tibia, proximal humerus, and fourth rib will be carefully examined to test the hypothesis that mice deficient in GDF 5, 6, or 7 will exhibit impaired endochondral bone growth. The proposed detailed analyses of stereologic and chondrocyte kinetic parameters will help to identify precisely which growth plate cell populations are affected by the absence of GDFs 5, 6, & 7. Future studies will extend these investigations to double and triple GDF family member mutations, as well as molecular characterization of other important growth plate signaling molecules in the various single, double, and triple GDF mutations.