Department of Internal Medicine, Hospital U.M. Valdecilla, IFIMAV, University of Cantabria, Santander, Spain.
Calcif Tissue Int. 2011 Oct;89(4):327-34. doi: 10.1007/s00223-011-9522-0. Epub 2011 Aug 28.
Osteocytes play a central role in the regulation of bone remodeling. The aim of this study was to explore osteocyte function, and particularly the expression of SOST, a Wnt inhibitor, in patients with hip fractures. Serum sclerostin levels were measured by ELISA. The expression of several osteocytic genes was studied by quantitative PCR in trabecular samples of the femoral head of patients with hip fractures, hip osteoarthritis and control subjects. The presence of sclerostin protein and activated caspase 3 was revealed by immunostaining. There were no significant differences in serum sclerostin between the three groups. Patients with fractures have fewer lacunae occupied by osteocytes (60 ± 5% vs. 64 ± 6% in control subjects, P = 0.014) and higher numbers of osteocytes expressing activated caspase 3, a marker of apoptosis. The proportion of sclerostin-positive lacunae was lower in patients with fractures than in control subjects (34 ± 11% vs. 69 ± 10%, P = 2 × 10(-8)). The proportion of sclerostin-positive osteocytes was also lower in patients. RNA transcripts of SOST, FGF23 and PHEX were also less abundant in fractures than in control bones (P = 0.002, 5 × 10(-6), and 0.04, respectively). On the contrary, in patients with osteoarthritis, there was a decreased expression of SOST and FGF23, without differences in PHEX transcripts or osteocyte numbers. Osteocyte activity is altered in patients with hip fractures, with increased osteocyte apoptosis and reduced osteocyte numbers, as well as decreased transcription of osteocytic genes. Therefore, these results suggest that an osteocyte deficiency may play a role in the propensity to hip fractures.
成骨细胞在骨重建的调节中起着核心作用。本研究旨在探讨成骨细胞的功能，特别是骨钙素抑制剂 SOST 的表达，在髋部骨折患者中的作用。采用 ELISA 法检测血清骨钙素水平。采用定量 PCR 方法研究髋部骨折、髋关节炎和对照组患者股骨头小梁样本中几种成骨细胞基因的表达。采用免疫组化法检测骨钙素蛋白和激活的 caspase 3 的存在。三组患者血清骨钙素水平无显著差异。骨折患者的骨陷窝中被成骨细胞占据的比例较少（60 ± 5%比对照组 64 ± 6%，P = 0.014），表达激活 caspase 3 的成骨细胞数量较多，这是凋亡的标志物。骨折患者的骨钙素阳性骨陷窝比例低于对照组（34 ± 11%比对照组 69 ± 10%，P = 2 × 10(-8)）。骨折患者的骨钙素阳性成骨细胞比例也较低。SOST、FGF23 和 PHEX 的 RNA 转录本在骨折患者中也低于对照组（P = 0.002、5 × 10(-6)和 0.04）。相反，在骨关节炎患者中，SOST 和 FGF23 的表达减少，但 PHEX 转录本或成骨细胞数量无差异。髋部骨折患者的成骨细胞活性发生改变，成骨细胞凋亡增加，成骨细胞数量减少，同时成骨细胞基因转录减少。因此，这些结果表明，成骨细胞缺乏可能在髋部骨折易感性中起作用。
