UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
未经授权:为了研究骨细胞β1整合素在骨中的体内功能,我们利用10kbDmp1(牙本质基质酸性磷蛋白1)-Cre在这种细胞类型中产生β1整合素缺失的小鼠。微型计算机断层扫描,进行骨组织形态计量学和免疫组织化学以确定骨细胞β1整合素丢失对骨质量累积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整合素在骨机械传导中的可能参与。
UNASSIGNED:骨细胞中β1整合素表达的丧失导致了严重的低骨量和负重长骨和棘的生物力学特性受损,但不是在非负重的颅骨,在老鼠身上。β1整合素的丢失导致腔隙-小管系统的尺寸增大,细胞形态异常,和骨细胞中的核脱臼。此外,β1整合素损失导致长骨中I型胶原纤维缩短和脱臼。骨细胞β1整合素的丢失不影响破骨细胞的活性,但显着降低了成骨细胞的骨形成率,同时,增强了骨髓基质细胞在骨骼微环境中的成脂分化。此外,胫骨负荷未能加速突变小鼠的合成代谢骨形成和改善I型胶原纤维完整性.
未经证实:我们的研究证明了骨细胞β1整合素在调节骨稳态和机械传导中的重要作用。本文的跨国潜力:本研究揭示了骨细胞β1整合素在体内维持骨量积累的调节作用,生物力学特性,细胞外基质完整性以及骨力学生物学,它定义了β1整合素是骨骼疾病的潜在治疗靶标,比如骨质疏松症。