Oxygen tension is an important mediator of the transformation of osteoblasts to osteocytes
Oxygen tension is an important mediator of the transformation of osteoblasts to osteocytes
复制标题
DOI：
10.1007/s00774-007-0765-9
复制
发表时间：
2007-09-01
影响因子：
3.3
通讯作者：
Yoshikawa, Hideki
中科院分区：
文献类型：
--
作者：
Hirao, Makoto;Hashimoto, Jun;Yoshikawa, Hideki
骨细胞来源于成骨细胞，但在缺氧条件下存在于矿化的骨基质中。与成骨细胞样细胞相比，成骨细胞样细胞表现出更高的ORP 150表达，这是由缺氧诱导的。因此，我们推测氧分压可能调节成骨细胞向骨细胞的转化。在常氧（20%O-2）和低氧（5%O-2）条件下培养MC 3 T3-E1细胞和来自4日龄小鼠的颅骨。为了研究成骨细胞分化和向骨细胞转化，进行茜素红染色，并评估各种因子的表达。低氧培养促进MC 3 T3-E1细胞矿化基质合成增加。碱性磷酸酶活性最初在低氧培养过程中增加，但在成骨过程中下降。骨钙素的产生也增加了低氧培养，但矿化后下降。此外，表达的Dmp 1，Mepe，Fgf 23，和Cx43，这是骨细胞特异性或骨细胞占主导地位的蛋白质，由MC 3 T3-E1细胞在低氧条件下比在常氧条件下更大。在小鼠颅骨培养物中，缺氧增加了骨基质中的细胞和表达Dmp 1和Mepe的细胞的数量。在MC 3 T3-E1细胞培养物中，ORP 150的表达仅在常氧条件下的矿化结节中检测到，而其表达在缺氧条件下是弥漫性的，这表明即使在常氧培养物中，结节也是缺氧区。这些结果表明，低氧张力促进成骨细胞分化和随后的转化为骨细胞。
Osteocytes are derived from osteoblasts, but reside in the mineralized bone matrix under hypoxic conditions. Osteocyte-like cells show higher expression of ORP150, which is induced by hypoxia, than osteoblast-like cells. Accordingly, we hypothesized that the oxygen tension may regulate the transformation of osteoblasts to osteocytes. MC3T3-E1 cells and calvariae from 4-day-old mice were cultured under normoxic (20% O-2) or hypoxic (5% O-2) conditions. To investigate osteoblastic differentiation and tranformation to osteocytes, alizarin red staining was done and the expression of various factors was assessed. Hypoxic culture promoted the increased synthesis of mineralized matrix by MC3T3-E1 cells. Alkaline phosphatase activity was initially increased during hypoxic culture, but decreased during osteogenesis. Osteocalcin production was also increased by hypoxic culture, but decreased after mineralization. Furthermore, expression of Dmp1, Mepe, Fgf23, and Cx43, which are osteocyte-specific or osteocyte-predominant proteins, by MC3T3-E1 cells was greater under hypoxic than under normoxic conditions. In mouse calvarial cultures, the number of cells in the bone matrix and cells expressing Dmp1 and Mepe were increased by hypoxia. In MC3T3-E1 cell cultures, ORP150 expression was only detected in the mineralized nodules under normoxic conditions, while its expression was diffuse under hypoxic conditions, suggesting that the nodules were hypoxic zones even in normoxic cultures. These findings suggest that a low oxygen tension promotes osteoblastic differentiation and subsequent transformation to osteocytes.