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Mechanically induced Ca^(2+) oscillations in osteocytes release extracellular vesicles and enhance bone formation 被引量:16
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作者 Andrea E.Morrell Genevieve N.Brown +8 位作者 Samuel T.Robinson Rachel L.Sattler Andrew D.Baik Gehua Zhen Xu Cao Lynda F.Bonewald Weiyang Jin Lance C.Kam x.edward guo 《Bone Research》 SCIE CAS CSCD 2018年第1期72-82,共11页
The vast osteocytic network is believed to orchestrate bone metabolic activity in response to mechanical stimuli through production of sclerostin, RANKL, and osteoprotegerin(OPG). However, the mechanisms of osteocyte ... The vast osteocytic network is believed to orchestrate bone metabolic activity in response to mechanical stimuli through production of sclerostin, RANKL, and osteoprotegerin(OPG). However, the mechanisms of osteocyte mechanotransduction remain poorly understood. We've previously shown that osteocyte mechanosensitivity is encoded through unique intracellular calcium (Ca^(2+) ) dynamics. Here, by simultaneously monitoring Ca^(2+) and actin dynamics in single cells exposed to fluid shear flow, we detected actin network contractions immediately upon onset of flow-induced Ca^(2+) transients, which were facilitated by smooth muscle myosin and further confirmed in native osteocytes ex vivo. Actomyosin contractions have been linked to the secretion of extracellular vesicles(EVs), and our studies demonstrate that mechanical stimulation upregulates EV production in osteocytes through immunostaining for the secretory vesicle marker Lysosomal-associated membrane protein 1(LAMP1) and quantifying EV release in conditioned medium, both of which are blunted when Ca^(2+) signaling was inhibited by neomycin. Axial tibia compression was used to induce anabolic bone formation responses in mice, revealing upregulated LAMP1 and expected downregulation of sclerostin in vivo. This load-related increase in LAMP1 expression was inhibited in neomycin-injected mice compared to vehicle.Micro-computed tomography revealed significant load-related increases in both trabecular bone volume fraction and cortical thickness after two weeks of loading, which were blunted by neomycin treatment. In summary, we found mechanical stimulation of osteocytes activates Ca^(2+) -dependent contractions and enhances the production and release of EVs containing bone regulatory proteins. Further, blocking Ca^(2+) signaling significantly attenuates adaptation to mechanical loading in vivo, suggesting a critical role for Ca^(2+) -mediated signaling in bone adaptation. 展开更多
关键词 OPG conditioned medium Ca2+-dependent
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Trabecular Plate Loss and Deteriorating Elastic Modulus of Femoral Trabecular Bone in Intertrochanteric Hip Fractures 被引量:5
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作者 Ji Wang Bin Zhou +4 位作者 Ian Parkinson C.David L.Thomas John G.Clement Nick Fazzalari x.edward guo 《Bone Research》 SCIE CAS 2013年第4期346-354,共9页
Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-compu... Osteoporotic hip fracture is associated with significant trabecular bone loss, which is typically characterized as low bone density by dual-energy X-ray absorptiometry (DXA) and altered microstructure by micro-computed tomography (pCT). Emerging morphological analysis techniques, e.g. individual trabecula segmentation (ITS), can provide additional insights into changes in plate-like and rod-like trabeculae, two major micro- structural types serving different roles in determining bone strength. Using ITS, we evaluated trabecular microstructure of intertrochanteric bone cores obtained from 23 patients undergoing hip replacement surgery for intertrochanteric fracture and 22 cadaveric controls. Micro-finite element (~FE) analyses were performed to further understand how the abnormalities seen by ITS might translate into effects on bone strength. ITS analyses revealed that, near fracture site, plate-like trabeculae were seriously depleted in fracture patients, but trabecular rod volume was maintained. Besides, decreased plate area and rod length were observed in fracture patients. Fracture patients also showed decreased elastic moduli and shear moduli of trabecular bone. These results provided evidence that in intertrochanteric hip fracture, preferential loss of plate-like trabeculae led to more rod-like microstructure and deteriorated mechanical competence adjacent to the fracture site, which increased our understanding of the biomechanical pathogenesis of hip fracture in osteoporosis. 展开更多
关键词 hip fracture INTERTROCHANTERIC microstructure individual trabecula segmentation finite element
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Intracellular calcium signaling in osteocytes:A mechano-transduction-mechano paradigm
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作者 Da Jing X.Lucas Lu +4 位作者 Andrew Baik Bin Zhou Xiaonan Lai Liyun Wang x.edward guo 《医用生物力学》 EI CAS CSCD 北大核心 2013年第S1期23-24,共2页
Osteocytes in vivo are embedded in the mineralized extracellular bone matrix,where their cell bodies reside in the lacunae and are interconnected to neighboring osteocytes through numerous intercellular processes.The ... Osteocytes in vivo are embedded in the mineralized extracellular bone matrix,where their cell bodies reside in the lacunae and are interconnected to neighboring osteocytes through numerous intercellular processes.The 3-dimensional(3D)osteocyte network positioning and ability to communicate with other bone cells make osteocytes ideal mechanosensors of bone.Thus the role of osteocyte network and intercellular communication between osteocytes in response to mechanical stimulation may clarify the mechanisms behind normal bone adaptation to mechanical loading.We have been using intracellular calcium([Ca<sup>2+</sup>]<sub>i</sub>)as a ubiquitous real-time signaling indicator for studying mechanotransduction in osteocytic network 展开更多
关键词 INTERCELLULAR transduction communicate stimulation signaling clarify NUMEROUS INTRACELLULAR PARADIGM positioning
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How does Mechanical Loading Make Bone Microstructure: Modeling vs. Remodeling
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作者 Samuel T.Robinson Yizhong Hu x.edward guo 《医用生物力学》 EI CAS CSCD 北大核心 2019年第A01期11-11,共1页
Bone modeling and remodeling are governed by distinct biochemical processes that may hold unique opportunities for optimizing bone mass[1,2].Remodeling refers to the coupled resorption and subsequent formation on the ... Bone modeling and remodeling are governed by distinct biochemical processes that may hold unique opportunities for optimizing bone mass[1,2].Remodeling refers to the coupled resorption and subsequent formation on the bone surface,while modeling represents uncoupled formation or resorption.Mechanical loading is known to improve bone mass,though whether this occurs through modeling or remodeling(or by some combination)is unclear.Dynamic in vivo morphometry utilizing high resolution micro-CT and image registration has only recently become feasible and thus holds an untapped and expanding potential for understanding bone metabolism by quantifying and localizing formation/resorption and modeling/remodeling events.16-week-old mice were given 2 baseline weekly micro-CT scans of both tibiae prior to the initiation of daily unilateral loading(contralateral limb for nonloaded control).Weekly scanning and daily loading continued for 5 weeks.Registered images for each mouse in a global coordinate system revealed the time course of each voxel,and changes in bone mass were quantified as modeling or remodeling starting at the onset of loading.In cortical bone,after an initial response to loading in both regimes,modeling emerged as the dominant response.Loading effects were largest in areas of mechanical significance.For example,anabolic modeling on the periosteal surface of the half of the tibia in compression under axial load presented a strong effect of loading,whereas the same measure on the endosteal surface in the area in tension showed no difference.Similarly,in trabecular bone anabolic modeling was significantly increased with loading on trabecular plates but not rods(plates have been shown to be the major contributor to overall bone strength).The catabolic modeling response on the endosteal surface showed an interesting transition over time.Loading initially led to a significant suppression of catabolic modeling,but over time increased it to levels significantly beyond that of nonloaded controls. 展开更多
关键词 Mechanical Loading MAKE BONE Microstructure MODELING VS REMODELING
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应力作用下骨细胞钙信号响应及转导的机制研究
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作者 刘曦雨 颜泽栋 +5 位作者 邵希 王丹 杨永青 罗二平 x.edward guo 景达 《医用生物力学》 CAS CSCD 北大核心 2021年第S01期462-462,共1页
目的骨能调节其结构以适应外界应力变化,但骨适应机理仍不明确。近年研究发现,骨细胞(OCY)是骨中核心力学响应细胞,但OCY如何响应和转导外界应力刺激仍不清楚。方法使用微接触压印自组装技术构建体外OCY和成骨细胞(OB)网络,观察流体剪切... 目的骨能调节其结构以适应外界应力变化,但骨适应机理仍不明确。近年研究发现,骨细胞(OCY)是骨中核心力学响应细胞,但OCY如何响应和转导外界应力刺激仍不清楚。方法使用微接触压印自组装技术构建体外OCY和成骨细胞(OB)网络,观察流体剪切力(FSS)下钙信号特征;构建新型小鼠胫骨原位OCY钙成像平台。 展开更多
关键词 流体剪切力 成骨细胞 自组装技术 钙成像 信号响应 适应机理 微接触压印 力学响应
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Calcium signaling in osteocyte network
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作者 X.Lucas Lu Andrew D.Baik +1 位作者 Victor Chiang x.edward guo 《医用生物力学》 EI CAS CSCD 2010年第S1期22-24,共3页
Introduction Osteocytes are interconnected through numerous intercellular processes,forming extensive cell networks throughout the bone tissue[1]. It has been shown that osteocyte density is an important physiological... Introduction Osteocytes are interconnected through numerous intercellular processes,forming extensive cell networks throughout the bone tissue[1]. It has been shown that osteocyte density is an important physiological parameter,which decreases 展开更多
关键词 AFM BONE cell MEM MLO EMD
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