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Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes

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TypeOfResource
Text
TitleInfo
Title
Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes
Identifier (type = pmcid)
PMC4915221
Name (type = personal)
NamePart (type = family)
Cheung
NamePart (type = given)
Wing Yee
Affiliation
City College of New York
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal); (authority = orcid); (authorityURI = http://id.loc.gov/vocabulary/identifiers/orcid.html); (valueURI = http://orcid.org/0000-0002-6475-7622)
NamePart (type = family)
Fritton
NamePart (type = given)
J. Christopher
Affiliation
Orthopaedics, Rutgers University
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Morgan
NamePart (type = given)
Stacy Ann
Affiliation
City College of New York
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Seref-Ferlengez
NamePart (type = given)
Zeynep
Affiliation
City College of New York
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Basta-Pljakic
NamePart (type = given)
Jelena
Affiliation
City College of New York
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Thi
NamePart (type = given)
Mia M.
Affiliation
Albert Einstein College of Medicine and Montefiore Medical Center
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Suadicani
NamePart (type = given)
Sylvia O.
Affiliation
Albert Einstein College of Medicine and Montefiore Medical Center
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Spray
NamePart (type = given)
David C.
Affiliation
Albert Einstein College of Medicine and Montefiore Medical Center
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Majeska
NamePart (type = given)
Robert J.
Affiliation
City College of New York
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = personal)
NamePart (type = family)
Schaffler
NamePart (type = given)
Mitchell B.
Affiliation
City College of New York
Role
RoleTerm (type = text); (authority = marcrt)
author
Name (type = corporate); (authority = RutgersOrg-Department)
NamePart
Orthopaedics
Name (type = corporate); (authority = RutgersOrg-School)
NamePart
New Jersey Medical School (NJMS)
Genre (authority = RULIB-FS)
Article, Refereed
Genre (authority = NISO JAV)
Accepted Manuscript (AM)
Note (type = peerReview)
Peer reviewed
OriginInfo
DateIssued (encoding = w3cdtf); (keyDate = yes)
2016
Abstract (type = Abstract)
Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring “bystander” cells to initiate the remodeling process is unknown. Apoptosis has been shown to open pannexin-1 (Panx1) channels to release adenosine diphosphate (ATP) as a “find me” signal for phagocytic cells. To address whether apoptotic osteocytes use this signaling mechanism, we adapted the rat ulnar fatigue-loading model to reproducibly introduce microdamage into mouse cortical bone and measured subsequent changes in osteocyte apoptosis, receptor activator of NF-kB ligand (RANKL) expression and osteoclastic bone resorption in wild-type (WT; C57Bl/6) mice and in mice genetically deficient in Panx1 (Panx1KO). Mouse ulnar loading produced linear microcracks comparable in number and location to the rat model. WT mice showed increased osteocyte apoptosis and RANKL expression at microdamage sites at 3 days after loading and increased intracortical remodeling and endocortical tunneling at day 14. With fatigue, Panx1KO mice exhibited levels of microdamage and osteocyte apoptosis identical to WT mice. However, they did not upregulate RANKL in bystander osteocytes or initiate resorption. Panx1 interacts with P2X<sub>7</sub>R in ATP release; thus, we examined P2X<sub>7</sub>R-deficient mice and WT mice treated with P2X<sub>7</sub>R antagonist Brilliant Blue G (BBG) to test the possible role of ATP as a find-me signal. P2X<sub>7</sub>RKO mice failed to upregulate RANKL in osteocytes or induce resorption despite normally elevated osteocyte apoptosis after fatigue loading. Similarly, treatment of fatigued C57Bl/6 mice with BBG mimicked behavior of both Panx1 KO and P2X<sub>7</sub>RKO mice; BBG had no effect on osteocyte apoptosis in fatigued bone but completely prevented increases in bystander osteocyte RANKL expression and attenuated activation of resorption by more than 50%. These results indicate that activation of Panx1 and P2X<sub>7</sub>R are required for apoptotic osteocytes in fatigued bone to trigger RANKL production in neighboring bystander osteocytes and implicate ATP as an essential signal mediating this process.
Language
LanguageTerm (authority = ISO 639-3:2007); (type = text)
English
PhysicalDescription
InternetMediaType
application/pdf
Extent
20 p.
Subject (authority = local)
Topic
Osteocyte apoptosis
Subject (authority = local)
Topic
Pannexin 1
Subject (authority = local)
Topic
P2X7 Receptor
Subject (authority = local)
Topic
Bystander signaling
Subject (authority = local)
Topic
RANKL
Subject (authority = local)
Topic
Fatigue microdamage
Extension
DescriptiveEvent
Type
Citation
DateTime (encoding = w3cdtf)
2016
AssociatedObject
Name
Journal of Bone and Mineral Research
Type
Journal
Relationship
Has part
Detail
890-899
Identifier (type = volume and issue)
31(4)
Reference (type = url)
http://dx.doi.org/10.1002/jbmr.2740
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
National Institutes of Health
AssociatedEntity
Role
Originator
Name
Mitchell B. Schaffler
AssociatedObject
Type
Grant number
Name
AR041210
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
National Institutes of Health
AssociatedEntity
Role
Originator
Name
Mitchell B. Schaffler
AssociatedObject
Type
Grant number
Name
AR057139
AssociatedEntity
Role
Originator
Name
David C. Spray
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
National Institutes of Health
AssociatedEntity
Role
Originator
Name
Mia M. Thi
AssociatedObject
Type
Grant number
Name
DK091466
AssociatedEntity
Role
Originator
Name
Sylvia O. Suadicani
Extension
DescriptiveEvent
Type
Grant award
AssociatedEntity
Role
Funder
Name
National Institutes of Health
AssociatedEntity
Role
Originator
Name
Mia M. Thi
AssociatedObject
Type
Grant number
Name
DK081435
AssociatedEntity
Role
Originator
Name
Sylvia O. Suadicani
RelatedItem (type = host)
TitleInfo
Title
Fritton, J. Christopher
Identifier (type = local)
rucore30160500001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3CV4MRZ
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Rights

Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsEvent
Type
Permission or license
AssociatedObject
Type
License
Name
Multiple author license v. 1
Detail
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RightsDeclaration (AUTHORITY = FS); (TYPE = [FS] statement #1); (ID = rulibRdec0004)
Copyright for scholarly resources published in RUcore is retained by the copyright holder. By virtue of its appearance in this open access medium, you are free to use this resource, with proper attribution, in educational and other non-commercial settings. Other uses, such as reproduction or republication, may require the permission of the copyright holder.
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Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
Document
CreatingApplication
Version
1.4
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2016-03-29T13:22:03
DateCreated (point = end); (encoding = w3cdtf); (qualifier = exact)
2016-04-02T14:33:13
ApplicationName
Acrobat Distiller 9.0.0 (Windows); modified using iTextSharp 5.2.1 (c) 1T3XT BVBA
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