Voisin Muriel, McNamara Laoise M
Biomechanics Research Centre (BMEC), Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Ireland.
Anat Rec (Hoboken). 2015 Sep;298(9):1548-59. doi: 10.1002/ar.23173. Epub 2015 Jun 3.
Integrin-based (β3 ) attachments to the extracellular matrix (ECM) on osteocyte cell processes have recently been proposed to play an important role in facilitating osteocyte mechanosensation. However, it is not yet known whether integrin expression is altered in the mechanoregulatory osteocytes during osteoporosis. The objective of this study was to test the hypothesis that the expression of integrin-based mechanosensory complexes (β1 and β3 integrins) is altered as a direct response to estrogen deficiency, in an estrogen deficient animal model of osteoporosis. Four weeks post-operatively, immunohistochemistry was used to detect for β1 and β3 integrin subunits in bone tissue and marrow of ovariectomized (OVX; N = 4) and SHAM (N = 4) operated animals. A tartrate resistant acid phosphatase (TRAP) control stain was performed to quantify the presence of osteoclasts in the bone marrow and bone surfaces. Image analysis was performed to quantify expression patterns in different biological compartments, that is, bone marrow, endosteum, and cortical bone. Our results showed that β1 integrins were ubiquitously expressed throughout the bone and marrow, for both OVX and SHAM groups. β3 integrin subunit expression was lower in bone cells from osteoporotic animals compared to controls, whereas β3 expression in marrow cells did not differ significantly between groups. At the endosteum no difference was observed in β3 integrin subunit expression. As expected, the number of osteoclasts was higher in the OVX group validating an imbalance in bone remodeling. We propose that a reduction in β3 integrin expression in osteocytes might impair mechanosensation by bone cells during estrogen deficiency.
最近有人提出,骨细胞突起上基于整合素(β3)与细胞外基质(ECM)的附着在促进骨细胞机械传感方面发挥重要作用。然而,目前尚不清楚在骨质疏松症期间,机械调节性骨细胞中的整合素表达是否会发生改变。本研究的目的是在骨质疏松症雌激素缺乏动物模型中,验证整合素介导的机械感觉复合物(β1和β3整合素)的表达作为对雌激素缺乏的直接反应而发生改变这一假设。术后四周,采用免疫组织化学方法检测去卵巢(OVX;N = 4)和假手术(N = 4)动物的骨组织和骨髓中的β1和β3整合素亚基。进行抗酒石酸酸性磷酸酶(TRAP)对照染色,以量化骨髓和骨表面破骨细胞的存在情况。进行图像分析以量化不同生物区室(即骨髓、骨内膜和皮质骨)中的表达模式。我们的结果表明,OVX组和假手术组的β1整合素在整个骨骼和骨髓中均普遍表达。与对照组相比,骨质疏松动物骨细胞中的β3整合素亚基表达较低,而骨髓细胞中β3的表达在各组之间无显著差异。在骨内膜,β3整合素亚基表达未观察到差异。正如预期的那样,OVX组的破骨细胞数量更高,证实了骨重塑的失衡。我们认为,雌激素缺乏期间骨细胞中β3整合素表达的降低可能会损害骨细胞的机械传感功能。