CCN 家族蛋白在成骨细胞分化过程中的不同作用：Smad 和 MAPK 信号通路的参与,Bone

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CCN 家族蛋白在成骨细胞分化过程中的不同作用：Smad 和 MAPK 信号通路的参与
Bone ( IF 3.5 ) Pub Date : 2011-11-01 , DOI: 10.1016/j.bone.2011.06.033
Harumi Kawaki ₁ , Satoshi Kubota , Akiko Suzuki , Makoto Suzuki , Kumiko Kohsaka , Kenji Hoshi , Toshiya Fujii , Noureddine Lazar , Toshihiro Ohgawara , Takeyasu Maeda , Bernard Perbal , Teruko Takano-Yamamoto , Masaharu Takigawa

Affiliation

CCN 家族蛋白在细胞过程的许多方面发挥着不同的作用，例如增殖、分化、粘附、迁移、血管生成和存活。在脊椎动物物种的骨组织中，已在成骨细胞中观察到大多数 CCN 家族成员的表达。然而，它们的空间和时间分布，以及它们的功能，仍然只是部分了解。在这项研究中，我们评估了 CCN 家族成员在体内骨骼组织中的定位，并比较分析了原代培养的小鼠成骨细胞中成员的基因表达模式和功能。免疫荧光分析显示 CCN 家族成员在成骨细胞和骨细胞中产生差异。在这些成骨细胞中证实了所有 Ccn 转录物的存在。成员中，CCN1、CCN2、在骨细胞中发现了 CCN4 和 CCN5。CCN4和CCN5也分布在位于骨基质内部的骨细胞中。接下来，我们研究了 Ccn 家族成员在成骨细胞分化过程中的表达模式。随着分化，大多数成员遵循适当的基因表达模式；而 Ccn4 和 Ccn5 表现出非常相似的模式。此外，我们通过使用重组 CCN 蛋白和 RNA 干扰方法评估了 CCN 家族成员对成骨细胞活性的影响。该家族的五个成员对成骨细胞增殖或分化显示出积极影响。值得注意的是，CCN3 显着抑制了成骨细胞的活性。每个 Ccn 特异性 siRNA 可以以观察到的各个重组 CCN 蛋白的作用所预期的方式调节成骨细胞活性。此外，我们发现细胞外信号调节激酶 1/2 和 p38 丝裂原活化蛋白激酶途径与 CCN 家族成员介导的成骨细胞活性修饰密切相关。总的来说，发现所有 Ccn 家族成员随着分化而差异表达，因此可以参与成骨细胞谱系的进展。

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Differential roles of CCN family proteins during osteoblast differentiation: Involvement of Smad and MAPK signaling pathways

CCN family proteins play diverse roles in many aspects of cellular processes such as proliferation, differentiation, adhesion, migration, angiogenesis and survival. In the bone tissue of vertebrate species, the expression of most CCN family members has been observed in osteoblasts. However, their spatial and temporal distributions, as well as their functions, are still only partially understood. In this study, we evaluated the localization of CCN family members in skeletal tissue in vivo and comparatively analyzed the gene expression patterns and functions of the members in murine osteoblasts in primary culture. Immunofluorescent analyses revealed that the CCN family members were differentially produced in osteoblasts and osteocytes. The presence of all Ccn transcripts was confirmed in those osteoblasts. Among the members, CCN1, CCN2, CCN4 and CCN5 were found in osteocytes. CCN4 and CCN5 were distributed in osteocytes located inside of bone matrix as well. Next, we investigated the expression pattern of Ccn family members during osteoblast differentiation. Along with differentiation, most of the members followed proper gene expression patterns; whereas, Ccn4 and Ccn5 showed quite similar patterns. Furthermore, we evaluated the effects of CCN family members on the osteoblastic activities by using recombinant CCN proteins and RNA interference method. Five members of this family displayed positive effects on osteoblast proliferation or differentiation. Of note, CCN3 drastically inhibited the osteoblast activities. Each Ccn specific siRNA could modulate osteoblast activities in a manner expected by the observed effect of respective recombinant CCN protein. In addition, we found that extracellular signal-regulated kinase1/2 and p38 mitogen-activated protein kinase pathways were critically involved in the CCN family member-mediated modification of osteoblast activities. Collectively, all Ccn family members were found to be differentially expressed along with differentiation and therefore could participate in progression of the osteoblast lineage.

更新日期：2011-11-01

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