Background

The key focal adhesion protein β1 integrin plays an essential role in early skeletal development. However, roles of β1 integrin expression in osteocytes during the regulation of bone homeostasis and mechanotransduction are incompletely understood.

Materials and methods

To study the in vivo function of osteocyte β1 integrin in bone, we utilized the 10-kb Dmp1 (Dentin matrix acidic phosphoprotein 1)-Cre to generate mice with β1 integrin deletion in this cell type. Micro-computerized tomography, bone histomorphometry and immunohistochemistry were performed to determine the effects of osteocyte β1 integrin loss on bone mass accrual and biomechanical properties. In vivo tibial loading model was applied to study the possible involvement of osteocyte β1 integrin in bone mechanotransduction.

Results

Loss of β1 integrin expression in osteocytes resulted in a severe low bone mass and impaired biomechanical properties in load-bearing long bones and spines, but not in non-weight-bearing calvariae, in mice. The loss of β1 integrin led to enlarged size of lacunar-canalicular system, abnormal cell morphology, and disorientated nuclei in osteocytes. Furthermore, β1 integrin loss caused shortening and disorientated collagen I fibers in long bones. Osteocyte β1 integrin loss did not impact the osteoclast activities, but significantly reduced the osteoblast bone formation rate and, in the meantime, enhanced the adipogenic differentiation of the bone marrow stromal cells in the bone microenvironment. In addition, tibial loading failed to accelerate the anabolic bone formation and improve collagen I fiber integrity in mutant mice.

Conclusions

Our studies demonstrate an essential role of osteocyte β1 integrin in regulating bone homeostasis and mechanotransduction.

The transnational potential of this article: This study reveals the regulatory roles of osteocyte β1 integrin in vivo for the maintenance of bone mass accrual, biomechanical properties, extracellular matrix integrity as well as bone mechanobiology, which defines β1 integrin a potential therapeutic target for skeletal diseases, such as osteoporosis.

中文翻译：

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骨细胞β1整合素丢失导致小鼠骨量低并损害骨力转导

 背景

关键的粘着斑蛋白β1整合素在早期骨骼发育中发挥着重要作用。然而，骨细胞中β1整合素表达在骨稳态和力传导调节过程中的作用尚不完全清楚。

 材料和方法

为了研究骨中骨细胞 β1 整合素的体内功能，我们利用 10-kb Dmp1（牙本质基质酸性磷蛋白 1）-Cre生成了这种细胞类型中 β1 整合素缺失的小鼠。通过微型计算机断层扫描、骨组织形态测量和免疫组织化学来确定骨细胞β1整合素丢失对骨量增长和生物力学特性的影响。应用体内胫骨负荷模型研究骨细胞β1整合素在骨力传导中的可能参与。

 结果

在小鼠中，骨细胞中β1整合素表达的丧失会导致承重长骨和脊柱的骨量严重降低和生物力学特性受损，但不会导致非承重颅盖骨的生物力学特性受损。 β1整合素的缺失导致腔隙-小管系统尺寸增大、细胞形态异常以及骨细胞中的细胞核定向障碍。此外，β1 整合素丢失导致长骨中 I 型胶原纤维缩短和定向。骨细胞β1整合素丢失并不影响破骨细胞活性，但显着降低成骨细胞骨形成率，同时增强骨微环境中骨髓基质细胞的成脂分化。此外，胫骨负重未能加速突变小鼠的合成代谢骨形成并改善 I 型胶原纤维的完整性。

 结论

我们的研究证明了骨细胞 β1 整合素在调节骨稳态和力传导中的重要作用。

本文的跨国潜力：这项研究揭示了骨细胞β1整合素在体内对维持骨量增长、生物力学特性、细胞外基质完整性以及骨力学生物学的调节作用，这将β1整合素定义为骨骼疾病的潜在治疗靶点，如骨质疏松症。