Osteocyte
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Osteocyte
The mechanosensors of bone orchestrate bone formation and bone resorption in accordance to external mechanical laoding.
Curated by Aviral Vatsa
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Arthritis Research & Therapy | Abstract | Impact of extracellular ...

Our recent study indicated that subchondral bone pathogenesis in osteoarthritis (OA) is associated with osteocyte morphology and phenotypic abnormalities. However, the mechanism underlying this abnormality needs to be ...
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Abstract (provisional)Introduction

Our recent study indicated that subchondral bone pathogenesis in osteoarthritis (OA) is associated with osteocyte morphology and phenotypic abnormalities. However, the mechanism underlying this abnormality needs to be identified. In this study we investigated the effect of extracellular matrix (ECM) produced from normal and OA bone on osteocytic cells function.

Methods

De-cellularized matrices, resembling the bone provisional ECM secreted from primary human subchondral bone osteoblasts (SBOs) of normal and OA patients were used as a model to study the effect on osteocytic cells. Osteocytic cells (MLOY4 osteocyte cell line) cultured on normal and OA derived ECMs were analyzed by confocal microscopy, scanning electron microscopy (SEM), cell attachment assays, zymography, apoptosis assays, qRT-PCR and western blotting. The role of integrinbeta1 and focal adhesion kinase (FAK) signalling pathways during these interactions were monitored using appropriate blocking antibodies.

Results

The ECM produced by OA SBOs contained less mineral content, showed altered organization of matrix proteins and matrix structure compared with the matrices produced by normal SBOs. Culture of osteocytic cells on these defective OA ECM resulted in a decrease of integrinbeta1 expression and the de-activation of FAK cell signaling pathway, which subsequently affected the initial osteocytic cell's attachment and functions including morphological abnormalities of cytoskeletal structures, focal adhesions, increased apoptosis, altered osteocyte specific gene expression and increased MMP-2 and -9 expression.

Conclusion

This study provides new insights in understanding how altered OA bone matrix can lead to the abnormal osteocyte phenotypic changes, which is typical in OA pathogenesis.

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E-selectin ligand-1 regulates bone remodeling by limiting bioactive TGF-β in the bone microenvironment « Osteoscoop - Servier

E-selectin ligand-1 regulates bone remodeling by limiting bioactive TGF-β in the bone microenvironment « Osteoscoop - Servier | Osteocyte | Scoop.it
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PLOS ONE: The Role of Osteocytes in Targeted Bone Remodeling: A Mathematical Model

PLOS ONE: The Role of Osteocytes in Targeted Bone Remodeling: A Mathematical Model | Osteocyte | Scoop.it
PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
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Myelopoiesis is regulated by osteocytes through Gsα-dependent ...

Myelopoiesis is regulated by osteocytes through Gsα-dependent ... | Osteocyte | Scoop.it
Key Points. Deletion of Gsα in osteocytes induces severe osteopenia and a dramatic expansion of cells of the myeloid lineage. Osteocytes regulate hematopoiesis and specifically contribute to myelopoiesis by secreting ...
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Mechanosensation and mechanotransduction: our connection to the outside world

Mechanosensation and mechanotransduction: our connection to the outside world | Osteocyte | Scoop.it
Author: Aviral Vatsa PhD MBBS This is the first post in a series of posts on mechanosensation and mechanotransduction and their role in physiology and disease.
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Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone.

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AbstractPURPOSE:

The purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes.

METHODS:

Proximal femur specimens were obtained following a total hip replacement procedure from men and women≥65years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6μm2) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive x-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student's t-test for normally distributed data and Mann-Whitney U-test for non-normally distributed data. An alpha value of<0.05 was considered significant.

RESULTS:

Thirty-five Caucasian participants were recruited (mean±standard deviation [SD] age, 75.5±6.5years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5±7.4years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36±0.98 wt % Ca versus 19.40±1.07 wt % Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99-4.12] wt % Ca versus 3.95±0.71 wt % Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12±0.97 wt % Ca for type 2 diabetes versus 20.44±1.30 wt % Ca for controls, p=0.121).

CONCLUSION:

The combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes.

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Osteocyte apoptosis

Osteocyte apoptosis | Osteocyte | Scoop.it
Bone, Volume null, Issue null, Pages null, null, Authors:Robert L. Jilka; Brendon Noble; Robert S.
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PLOS ONE: Osteocyte Network; a Negative Regulatory System for Bone Mass Augmented by the Induction of Rankl in Osteoblasts and Sost in Osteocytes at Unloading

PLOS ONE: Osteocyte Network; a Negative Regulatory System for Bone Mass Augmented by the Induction of Rankl in Osteoblasts and Sost in Osteocytes at Unloading | Osteocyte | Scoop.it
PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
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Actin cap associated focal adhesions and their distinct role in cellular mechanosensing

Reporter: Aviral Vatsa
A new study in Scientific Reports by Dong Hwee Kim et al has demonstrated the role of actin cap associated focal adhesions in mechanosensing.
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Nitric Oxide and Immune responses: part 1

Nitric Oxide and Immune responses: part 1 | Osteocyte | Scoop.it
Curator/Reporter Aviral Vatsa PhD, MBBS Based on: A review by Wink et al., 2011 This is the first part of a two part post Nitric oxide (NO), reactive nitrogen species (RNS) and reactive oxygen species (ROS) perform dual roles as immunotoxins and...
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SSRIs: Bad to the Bone?

Based
on SSRIs:
Bad to the Bone?
(Sansone
and Sansone, 2012)
Abstract
Selective
serotonin reuptake inhibitors are globally popular antidepressants
with broad clinical indications.
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Perspectives on Nitric Oxide in Disease Mechanisms

Perspectives on Nitric Oxide in Disease Mechanisms | Osteocyte | Scoop.it

Perspectives on Nitric Oxide in Disease Mechanisms The Nitric Oxide Discovery, Function, and Targeted Therapy  OpportunitiesFrom Discovery to Innovation     From Innovation Therapeutic TargetsFrom Innovation Targets to Clinical Applications Aviral Vatsa, PhD, EditorLeaders in Pharmaceutical Business Intelligence, Scotlandaviralvatsa@gmail.comandLarry H Bernstein, MD, EditorTriplex Medical Science, Trumbull, CTLarry.bernstein@gmail.com Leaders in Pharmaceutical Business IntelligenceAviva Lev-Ari, PhD, RNDirector and FounderEditor-in-Chief

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Beauty of science: Osteocyte lacuno ...

Beauty of science: Osteocyte lacuno ... | Osteocyte | Scoop.it
Based on a sample from the femur of a 92-year-old female, it shows for the first time over a large field of view the 3D “osteocyte lacuno-canalicular network” – a complex mesh of holes and channels embedded in mineralised ...
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Dynamic permeability of the lacunar–canalicular system in human cortical bone - Online First - Springer

Dynamic permeability of the lacunar–canalicular system in human cortical bone - Online First - Springer | Osteocyte | Scoop.it
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M. Benalla, P. E. Palacio-Mancheno, S. P. Fritton, L. Cardoso, S. C. Cowin

Abstract

A new method for the experimental determination of the permeability of a small sample of a fluid-saturated hierarchically structured porous material is described and applied to the determination of the lacunar–canalicular permeability (KLC) in bone. The interest in the permeability of the lacunar–canalicular pore system (LCS) is due to the fact that the LCS is considered to be the site of bone mechanotransduction due to the loading-driven fluid flow over cellular structures. The permeability of this space has been estimated to be anywhere from 10−17 to 10−25m2 . However, the vascular pore system and LCS are intertwined, rendering the permeability of the much smaller-dimensioned LCS challenging to measure. In this study, we report a combined experimental and analytical approach that allowed the accurate determination of the KLC to be on the order of 10−22m2 for human osteonal bone. It was found that the KLC has a linear dependence on loading frequency, decreasing at a rate of 2×10−24m2 /Hz from 1 to 100 Hz, and using the proposed model, the porosity alone was able to explain 86 % of the KLC variability.

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Matrix-dependent adhesion mediates network responses to physiological stimulation of the osteocyte cell process

Aviral Vatsa's insight:
Abstract

Osteocytes are bone cells that form cellular networks that sense mechanical loads distributed throughout the bone tissue. Interstitial fluid flow in the lacunar canalicular system produces focal strains at localized attachment sites around the osteocyte cell process. These regions of periodic attachment between the osteocyte cell membrane and its canalicular wall are sites where pN-level fluid-flow induced forces are generated in vivo. In this study, we show that focally applied forces of this magnitude using a newly developed Stokesian fluid stimulus probe initiate rapid and transient intercellular electrical signals in vitro. Our experiments demonstrate both direct gap junction coupling and extracellular purinergic P2 receptor signaling between MLO-Y4 cells in a connected bone cell network. Intercellular signaling was initiated by pN-level forces applied at integrin attachment sites along both appositional and distal unapposed cell processes, but not initiated at their cell bodies with equivalent forces. Electrical coupling was evident in 58% of all cell pairs tested with appositional connections; coupling strength increased with the increasing number of junctional connections. Apyrase, a nucleotide-degrading enzyme, suppressed and abolished force-induced effector responses, indicating a contribution from ATP released by the stimulated cell. This work extends the understanding of how osteocytes modulate their microenvironment in response to mechanical signals and highlights mechanisms of intercellular relay of mechanoresponsive signals in the bone network.

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For the Sake of Inquiry and Knowledge — The Inevitability of Open Access — NEJM

For the Sake of Inquiry and Knowledge — The Inevitability of Open Access — NEJM | Osteocyte | Scoop.it
Perspective from The New England Journal of Medicine — For the Sake of Inquiry and Knowledge — The Inevitability of Open Access
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Myelopoiesis is regulated by osteocytes through Gsα-dependent ...

Myelopoiesis is regulated by osteocytes through Gsα-dependent ... | Osteocyte | Scoop.it
Key Points. Deletion of Gsα in osteocytes induces severe osteopenia and a dramatic expansion of cells of the myeloid lineage. Osteocytes regulate hematopoiesis and specifically contribute to myelopoiesis by secreting ...
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Osteocytes remove and replace perilacunar mineral during reproductive cycles

Osteocytes remove and replace perilacunar mineral during reproductive cycles | Osteocyte | Scoop.it
Bone, Volume null, Issue null, Pages null, null, Authors:John J. Wysolmerski
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Emerging role of primary cilia as mechanosensors in osteocytes

Emerging role of primary cilia as mechanosensors in osteocytes | Osteocyte | Scoop.it
Bone, Volume null, Issue null, Pages null, null, Authors:An M. Nguyen; Christopher R.
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Osteocytes: a special issue in Bone

Osteocytes: a special issue in Bone | Osteocyte | Scoop.it
Reporter and curator: Aviral Vatsa PhD, MBBS Osteocytes are the professional mechanosensors of bone.
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Targeted delivery of therapeutics to bone and connective tissues: current status and challenges- Part I

Targeted delivery of therapeutics to bone and connective tissues: current status and challenges- Part I | Osteocyte | Scoop.it
Reporter Aviral Vatsa, PhD MBBSAnnual treatment costs for musculoskeletal diseases in the US are roughly 7.7% (~ $849 billion) of total gross domestic product. Such disorders are the main cause of physical disability in US.
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Targeted delivery of therapeutics to bone and connective tissues: current status and challenges- Part II

Targeted delivery of therapeutics to bone and connective tissues: current status and challenges- Part II | Osteocyte | Scoop.it
 Curator/Reporter: Aviral Vatsa PhD MBBSThis post is in the second part of the reviews that focuses on the current status of drug delivery to bone and the issues facing this field.
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Overview of new strategy for treatment of T2DM: SGLT2 inhibiting oral antidiabetic agents

Overview of new strategy for treatment of T2DM: SGLT2 inhibiting oral antidiabetic agents | Osteocyte | Scoop.it
Author: Aviral Vatsa PhD MBBS
Type
2 diabetes mellitus (T2DM) is a chronic disease, which is affecting
widespread populations in epidemic proportions across the globe 1.
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Asic3 is a neuronal mechanosensor for pressure-induced vasodilation that protects against pressure ulcers | BioPortfolio.com

Asic3 is a neuronal mechanosensor for pressure-induced vasodilation that protects against pressure ulcers | BioPortfolio.com | Osteocyte | Scoop.it
From BioPortfolio: A slight mechanical pressure applied to healthy skin results in blood vessel dilation, preserving blood flow. Defects in this vasodilatory response lead to an i...
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