Non-functional Fas ligand increases the formation of cartilage early in the endochondral bone induction by rhBMP-2
Non-functional Fas ligand increases the formation of cartilage early in the endochondral bone induction by rhBMP-2
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DOI：
10.1016/j.lfs.2003.06.031
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发表时间：
2003-11-21
期刊：
影响因子：
6.1
通讯作者：
Marusic, A
中科院分区：
文献类型：
--
作者：
Katavic, V;Grcevic, D;Marusic, A
此前已有研究表明，Fas配体介导的细胞凋亡缺陷的小鼠可促进异位骨形成。我们研究了重组人(Rh)BMP-2诱导的小鼠异位新骨中碱性磷酸酶、胶原、骨涎蛋白、骨钙素、骨桥蛋白、骨形态发生蛋白(BMP)-2、-4和-7以及细胞因子白介素1α(IL-1α)、白介素1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的表达。植入rhBMP-2后第6天，与野生型相比，GLD小鼠形成了更多的软骨和间充质。在后期，GLD小鼠在新生组织体积上与对照组小鼠没有差异，BMP基因表达水平较高，而成骨细胞成熟相关基因-骨涎蛋白和骨桥蛋白表达水平较低。IL-1α和TNF-α的表达只有在植入rhBMP-2后12天才能观察到差异。这些结果表明，GLD小鼠间充质来源的细胞募集增加，新形成的间充质组织分化和成熟模式异常。(C)2003 Elsevier Inc.保留所有权利。
It has previously been shown that mice with a defect in Fas ligand-mediated apoptosis have an enhancement of ectopic bone formation. We investigated the expression of bone-related markers - alkaline phosphatase, collagen, bone sialoprotem, osteocalcin, osteopontin, and bone morphogenetic proteins (BMP) -2, -4, and -7; and cytokines interleukin-1alpha (IL-1), IL-1beta, and tumor necrosis factor-alpha (TNF-alpha) in ectopic new bone induced by recombinant human (rh) BMP-2 in mice without functional Fas-ligand (gld mice). At day 6 after rhBMP-2 implantation, gld mice formed more cartilage and mesenchyme compared with their wild type littermates. At later stages, gld mice did not differ from the control mice in the volume of newly formed tissue, expressing higher level of BMP genes and lower levels of genes involved in osteoblast maturation - bone sialoprotein and osteopontin. Differences in the levels of expression of IL-1alpha and TNF-alpha were observed only at day 12 after rhBMP-2 implantation. These results suggest that gld mice have an increased recruitment of cells of mesenchymal origin and an abnormal pattern of differentiation and maturation of the newly formed mesenchymal tissues. (C) 2003 Elsevier Inc. All rights reserved.