Tuftelin was originally discovered and mostly studied in the tooth, but later found also in other organs. Despite its wide distribution among tissues, tuftelin's function has so far been specified only in the formation of enamel crystals. Nevertheless, in many cases, tuftelin was suggested to be associated with cellular adaptation to hypoxia and recently even with cell differentiation. Therefore, we aimed to investigate tuftelin expression along with hypoxia-inducible factors (HIFs) during the early development of the mandibular/alveolar (m/a) bone, when osteoblasts started to differentiate in vivo and to compare their expression levels in undifferentiated versus differentiated osteoblastic cells in vitro. Immunohistochemistry demonstrated the presence of tuftelin already in osteoblastic precursors which were also HIF1-positive, but HIF2-negative. Nevertheless, HIF2 protein appeared when osteoblasts differentiated, one day later. This is in agreement with observations made with MC3T3-E1 cells, where there was no significant difference in tuftelin and Hif1 expression in undifferentiated vs. differentiated cells, although Hif2 increased upon differentiation induction. In differentiated osteoblasts of the m/a bone, all three proteins accumulated, first, prenatally, in the cytoplasm and later, particularly at postnatal stages, they displayed also peri/nuclear localization. Such a dynamic time-space pattern of tuftelin expression has recently been reported in neurons, which, as the m/a bone, differentiate under less hypoxic conditions as indicated also by a prevalent cytoplasmic expression of HIF1 in osteoblasts. However, unlike what was shown in cultured neurons, tuftelin does not seem to participate in final osteoblastic differentiation and its functions, thus, appears to be tissue specific.

中文翻译：

---

Tuftelin和HIFs在成骨中的表达。

Tuftelin最初被发现并且主要在牙齿中研究，但后来在其他器官中也被发现。尽管其在组织中分布广泛，但迄今仅在搪瓷晶体的形成中确定了图夫特林的功能。然而，在许多情况下，都暗示图夫特林与细胞对缺氧的适应性相关，最近甚至与细胞分化有关。因此，我们的目的是研究成骨细胞开始在体内分化的过程中，在下颌/牙槽骨（m / a）骨早期发育过程中，tuftelin的表达与缺氧诱导因子（HIFs）的关系，并比较其在未分化和分化状态下的表达水平。体外成骨细胞。免疫组织化学表明，在成骨细胞前体中也存在图夫特林，该前体也是HIF1阳性，但HIF2阴性。然而，一天后成骨细胞分化时出现了HIF2蛋白。这与MC3T3-E1细胞的观察结果一致，在MC3T3-E1细胞中，未分化和分化细胞中Tuftelin和Hif1表达没有显着差异，尽管Hif2在分化诱导后增加。在m / a骨的分化成骨细胞中，所有三种蛋白质首先在产前积累在细胞质中，然后再积累，特别是在出生后阶段，它们还表现出周/核定位。Tuftelin表达的这种动态时空模式最近在神经元中得到了报道，神经元作为m / a骨，在缺氧较少的条件下分化，这也由成骨细胞中HIF1的普遍细胞质表达所表明。但是，与培养的神经元所显示的不同，