Large magnitude of force leads to NO-mediated cell shrinkage in single osteocytes implying an initial apoptotic response

Nakao, N.; Mori, Izumi C.; Sunaga, Junko; Adachi, Taiji

doi:10.1016/j.jbiomech.2021.110245

Cited by 2 publications

(2 citation statements)

References 52 publications

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“…To precisely target the subcellular components, magnetic tweezers have been used (Alenghat, et al, 2000;Nakao, et al, 2021), in which an electromagnetic force is generated from the tip of a metal rod coiled with wire. To clarify the mechanism of osteocyte apoptosis caused by mechanical overload, the tweezer generated cyclic mechanical stimuli of 500 pN or 1000 pN to focal adhesions via fibronectin-coated magnetic microbeads (diameter: 4.5 μm) adhered to the cell surface in isolated osteocytes (Nakao, et al, 2021). The stimulation levels of 500 and 1000 pN mimicked normal and over-loading, respectively.…”

Section: Tools For Mechanical Stimulationmentioning

confidence: 99%

Investigation of mechanosensing and mechanoresponse mechanisms in osteoblasts and osteocytes: <i>in vitro</i> experiments targeting subcellular components

Nakao

Adachi

2022

JBSE

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To understand adaptive bone remodeling in response to external mechanical stimuli, researchers have elucidated the mechanisms of mechanosensing and mechanoresponse through in vitro experiments targeting subcellular components from molecules to organelles. Such subcellular experiments have been performed by applying mechanical stimuli to mechanosensitive components and by measuring and observing the dynamic behaviors of the mechanosensitive and mechanoresponsive components. For a better understanding of the importance of the subcellular experiments, this article reviews the recent subcellular experiments for osteoblasts and osteocytes. First, we introduce the tools used for the stimulation and measurement/observation, and we discuss how these tools have contributed to the elucidation of the mechanisms. Second, we shed light on how the findings on the behaviors of the subcellular components have enhanced our basic understanding of the underlying mechanisms. Furthermore, we present future perspectives for subcellular experiments. To do this, we discuss the utilization of microscopes with higher spatial resolution and discuss focus points for a clearer understanding of these mechanisms in osteocytes. Future experiments will reveal how osteoblasts and osteocytes sense and respond to external mechanical stimuli in their surrounding environment in bone, and how cellular behaviors finally lead to the regulation of bone resorption and formation in adaptive bone remodeling.

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Section: Tools For Mechanical Stimulationmentioning

confidence: 99%

Investigation of mechanosensing and mechanoresponse mechanisms in osteoblasts and osteocytes: <i>in vitro</i> experiments targeting subcellular components

Nakao

Adachi

2022

JBSE

Self Cite

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“…Nevertheless, sclerostin can be expressed by bone cells through mechanical loading and independently of PTH (Spatz et al, 2015). Furthermore, it is known that osteocyte apoptosis can be induced through mechanical loading (Hughes and Petit, 2010;Nakao et al, 2021). Such results highlight that osteocytes need to be in a quiescent state, or equilibrium state, and within the physiological strain window, even when considering their chemical regulator role.…”

Section: Osteocyte Perilacunar and Pericellular Matrices As Markers O...mentioning

confidence: 99%

Osteocyte pericellular and perilacunar matrices as markers of bone–implant mechanical integrity

Gauthier¹,

Follet²,

Trunfio-Sfarghiu³

et al. 2022

Biocell

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To develop durable bone healing strategies through improved control of bone repair, it is of critical importance to understand the mechanisms of bone mechanical integrity when in contact with biomaterials and implants. Bone mechanical integrity is defined here as the adaptation of structural properties of remodeled bone in regard to an applied mechanical loading. Accordingly, the authors present why future investigations in bone repair and regeneration should emphasize on the matrix surrounding the osteocytes. Osteocytes are mechanosensitive cells considered as the orchestrators of bone remodeling, which is the biological process involved in bone homeostasis. These bone cells are trapped in an interconnected porous network, the lacunocanalicular network, which is embedded in a bone mineralized extracellular matrix. As a consequence of an applied mechanical loading, the bone deformation results in the deformation of this lacunocanalicular network inducing a shift in interstitial fluid pressure and velocity, thus resulting in osteocyte stimulation.The material environment surrounding each osteocyte, the so called perilacunar and pericellular matrices properties, define its mechanosensitivity. While this mechanical stimulation pathway is well known, the laws used to predict bone remodeling are based on strains developing at a tissue scale, suggesting that these strains are related to the shift in fluid pressure and velocity at the lacunocanalicular scale. While this relationship has been validated through observation in healthy bone, the fluid behavior at the bone-implant interface is more complex. The presence of the implant modifies fluid behavior, so that for the same strain at a tissue scale, the shift in fluid pressure and velocity will be different than in a healthy bone tissue. In that context, new markers for bone mechanical integrity, considering fluid behavior, have to be defined. The viewpoint exposed by the authors indicates that the properties of the pericellular and the perilacunar matrices have to be systematically investigated and used as structural markers of fluid behavior in the course of bone biomaterial development.

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Large magnitude of force leads to NO-mediated cell shrinkage in single osteocytes implying an initial apoptotic response

Cited by 2 publications

References 52 publications

Investigation of mechanosensing and mechanoresponse mechanisms in osteoblasts and osteocytes: <i>in vitro</i> experiments targeting subcellular components

Investigation of mechanosensing and mechanoresponse mechanisms in osteoblasts and osteocytes: <i>in vitro</i> experiments targeting subcellular components

Osteocyte pericellular and perilacunar matrices as markers of bone–implant mechanical integrity

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