Department of Orthopaedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts, USA.
FASEB J. 2018 Jan;32(1):440-452. doi: 10.1096/fj.201700485RR. Epub 2017 Sep 19.
Osteocytes are master orchestrators of bone remodeling; they control osteoblast and osteoclast activities both directly cell-to-cell communication and indirectly secreted factors, and they are the main postnatal source of sclerostin and RANKL (receptor activator of NF-kB ligand), two regulators of osteoblast and osteoclast function. Despite progress in understanding osteocyte biology and function, much remains to be elucidated. Recently developed osteocytic cell lines-together with new genome editing tools-has allowed a closer look at the biology and molecular makeup of these cells. By using single-cell cloning, we identified genes that are associated with high Sost/sclerostin expression and analyzed their regulation and function. Unbiased transcriptome analysis of high- low-Sost/sclerostin-expressing cells identified known and novel genes. Dmp1 (dentin matrix protein 1), Dkk1 (Dickkopf WNT signaling pathway inhibitor 1), and Phex were among the most up-regulated known genes, whereas Srpx2, Cd200, and carbonic anhydrase III (CAIII) were identified as novel markers of differentiated osteocytes. Aspn, Enpp2, Robo2, Nov, and Serpina3g were among the transcripts that were most significantly suppressed in high-Sost cells. Considering that CAII was recently identified as being regulated by Sost/sclerostin and capable of controlling mineral homeostasis, we focused our attention on CAIII. Here, we report that CAIII is highly expressed in osteocytes, is regulated by parathyroid hormone both and , and protects osteocytes from oxidative stress.-Shi, C., Uda, Y., Dedic, C., Azab, E., Sun, N., Hussein, A. I., Petty, C. A., Fulzele, K., Mitterberger-Vogt, M. C., Zwerschke, W., Pereira, R., Wang, K., Divieti Pajevic, P. Carbonic anhydrase III protects osteocytes from oxidative stress.
成骨细胞是骨重塑的主要调控者；它们通过细胞间直接通讯和间接分泌因子来控制成骨细胞和破骨细胞的活性，并且是骨硬化蛋白和 RANKL（核因子 κB 配体受体激活剂）的主要出生后来源，这两种因子调节成骨细胞和破骨细胞的功能。尽管人们对成骨细胞的生物学和功能有了更多的了解，但仍有许多问题有待阐明。最近开发的成骨细胞系——以及新的基因组编辑工具——使人们能够更深入地研究这些细胞的生物学和分子构成。通过使用单细胞克隆，我们确定了与高 Sost/骨硬化蛋白表达相关的基因，并分析了它们的调控和功能。对高表达和低表达 Sost/骨硬化蛋白的细胞进行无偏转录组分析，确定了已知和新的基因。在高表达 Sost/骨硬化蛋白的细胞中，已知的上调基因包括 Dmp1（牙本质基质蛋白 1）、Dkk1（Dickkopf WNT 信号通路抑制剂 1）和 Phex，而 Srpx2、Cd200 和碳酸酐酶 III（CAIII）被鉴定为分化的成骨细胞的新标记物。在高 Sost 细胞中，Aspn、Enpp2、Robo2、Nov 和 Serpina3g 等转录物的表达受到显著抑制。考虑到 CAII 最近被鉴定为受 Sost/骨硬化蛋白调控并能够控制矿物质稳态，我们将注意力集中在 CAIII 上。在这里，我们报告 CAIII 在成骨细胞中高表达，受甲状旁腺激素的调控，无论是直接还是间接，并且能保护成骨细胞免受氧化应激。-Shi, C., Uda, Y., Dedic, C., Azab, E., Sun, N., Hussein, A. I., Petty, C. A., Fulzele, K., Mitterberger-Vogt, M. C., Zwerschke, W., Pereira, R., Wang, K., Divieti Pajevic, P. Carbonic anhydrase III protects osteocytes from oxidative stress.
