Mechanosensation and transduction in osteocytes

Klein‐Nulend, Jenneke; Bakker, Astrid D.; Bacabac, Rommel G.; Vatsa, A.; Weinbaum, Sheldon

doi:10.1016/j.bone.2012.10.013

Cited by 414 publications

(339 citation statements)

References 114 publications

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“…Despite osteocytes being regarded as the primary mechanosensors of bone, most previous studies have used osteoblasts. 8 One reason for this is because primary osteocytes are so difficult to isolate and culture owing to their position within bone. To date, only chick, 80,81 mouse [82][83][84] and rat 85 primary osteocytes have successfully been isolated using sequential bone digestion.…”

Section: Discussionmentioning

confidence: 99%

“…Osteocytes are regarded as the key mechanosensing cells of the bone that regulate the activity of osteoblasts and osteoclasts. 7,8 However, in vitro studies have shown that osteogenic progenitors, 9,10 osteoblasts 3,11,12 and osteoclasts 13,14 are capable of responding to loading. The changes in bone formation induced by mechanotransduction are termed adaptive remodeling.…”

Section: Introductionmentioning

confidence: 99%

“…The changes in bone formation induced by mechanotransduction are termed adaptive remodeling. 8 The aim of an in vitro loading model is to recreate the conditions required to engender mechanotransduction in a controlled cell culture environment. The specific objectives may vary from applying physiologically relevant levels of particular mechanical stimulation to exceeding the normal physiological conditions, which may represent pathological or induced states.…”

Section: Introductionmentioning

confidence: 99%

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Preclinical models for in vitro mechanical loading of bone-derived cells

Delaine-Smith¹,

Javaheri²,

Edwards³

et al. 2015

BoneKEy Reports

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It is well established that bone responds to mechanical stimuli whereby physical forces are translated into chemical signals between cells, via mechanotransduction. It is difficult however to study the precise cellular and molecular responses using in vivo systems. In vitro loading models, which aim to replicate forces found within the bone microenvironment, make the underlying processes of mechanotransduction accessible to the researcher. Direct measurements in vivo and predictive modeling have been used to define these forces in normal physiological and pathological states. The types of mechanical stimuli present in the bone include vibration, fluid shear, substrate deformation and compressive loading, which can all be applied in vitro to monolayer and three-dimensional (3D) cultures. In monolayer, vibration can be readily applied to cultures via a low-magnitude, high-frequency loading rig. Fluid shear can be applied to cultures in multiwell plates via a simple rocking platform to engender gravitational fluid movement or via a pump to cells attached to a slide within a parallel-plate flow chamber, which may be micropatterned for use with osteocytes. Substrate strain can be applied via the vacuum-driven FlexCell system or via a four-point loading jig. 3D cultures better replicate the bone microenvironment and can also be subjected to the same forms of mechanical stimuli as monolayer, including vibration, fluid shear via perfusion flow, strain or compression. 3D cocultures that more closely replicate the bone microenvironment can be used to study the collective response of several cell types to loading. This technical review summarizes the methods for applying mechanical stimuli to bone cells in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preclinical models for in vitro mechanical loading of bone-derived cells

Delaine-Smith¹,

Javaheri²,

Edwards³

et al. 2015

BoneKEy Reports

View full text Add to dashboard Cite

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“…Osteocytes areterminally differentiated osteoblasts that communicate with one another and form extensive networks such as neural cells, in bone tissue. Osteocytes play an important role as mechanosensory cells and contribute to keep bone homeostasis caused by bone loading (6,7). Furthermore, osteocytes may also regulate systemic homeostasis by mechanotransduction.Recently, novel roles of osteocytes were elucidated through "osteohematology."…”

Section: Introductionmentioning

confidence: 99%

Osteocytes and Homeostasis of Remote Organs

Sato

Katayama

2015

Curr Osteoporos Rep

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The study of bones has attracted researchers from many medical fields. To understand bone-organ interactions, hematologists were challenged to investigate bone marrow (BM), the core of bone where hematopoiesis takes place. Through studies of the hematopoietic stem cells niche, hematologists contributed to the discovery of unexpected functions of bone-forming osteoblasts and bone-buried osteocytes.Especially, the recent findings about osteocytes, as the regulatory system of lympho-hematopoiesis and fat metabolism, highlighted the central role of skeletal tissue in inter-organ communication. The cross-cutting consideration including hematology and many other fields will expand the bone research.

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“…The osteocyte network plays a master role in maintaining bone homeostasis through signaling pathways that orchestrate osteoblast and osteoclast activities necessary for normal bone health 2. Osteocyte cell death and alterations in dendritic morphology and connectivity play a role in osteonecrosis of the femoral head, especially following chronic steroid treatment 3.…”

mentioning

confidence: 99%

Osteocyte physiology and response to fluid shear stress are impaired following exposure to cobalt and chromium: Implications for bone health following joint replacement

et al. 2016

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The effects of metal ion exposure on osteocytes, the most abundant cell type in bone and responsible for coordinating bone remodeling, remain unclear. However, several studies have previously shown that exposure to cobalt (Co2+) and chromium (Cr3+), at concentrations equivalent to those found clinically, affect osteoblast and osteoclast survival and function. In this study, we tested the hypothesis that metal ions would similarly impair the normal physiology of osteocytes. The survival, dendritic morphology, and response to fluid shear stress of the mature osteocyte‐like cell‐line MLO‐Y4 following exposure to clinically relevant concentrations and combinations of Co and Cr ions were measured in 2D‐culture. Exposure of MLO‐Y4 cells to metal ions reduced cell number, increased dendrites per cell and increased dendrite length. We found that combinations of metal ions had a greater effect than the individual ions alone, and that Co2+ had a predominate effect on changes to cell numbers and dendrites. Combined metal ion exposure blunted the responses of the MLO‐Y4 cells to fluid shear stress, including reducing the intracellular calcium responses and modulation of genes for the osteocyte markers Cx43 and Gp38, and the signaling molecules RANKL and Dkk‐1. Finally, we demonstrated that in the late osteoblasts/early osteocytes cell line MLO‐A5 that Co2+ exposure had no effect on mineralization, but Cr3+ treatment inhibited mineralization in a dose‐dependent manner, without affecting cell viability. Taken together, these data indicate that metal exposure can directly affect osteocyte physiology, with potential implications for bone health including osseointegration of cementless components, and periprosthetic bone remodeling. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1716–1723, 2017.

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Mechanosensation and transduction in osteocytes

Cited by 414 publications

References 114 publications

Preclinical models for in vitro mechanical loading of bone-derived cells

Preclinical models for in vitro mechanical loading of bone-derived cells

Osteocytes and Homeostasis of Remote Organs

Osteocyte physiology and response to fluid shear stress are impaired following exposure to cobalt and chromium: Implications for bone health following joint replacement

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