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The Impact of Acetylcholine Receptors on Osteocytes and Bone Mechanoadaptation
The Impact of Acetylcholine Receptors on Osteocytes and Bone Mechanoadaptation
The Impact of Acetylcholine Receptors on Osteocytes and Bone Mechanoadaptation

상세정보

자료유형  
 학위논문 서양
최종처리일시  
20250211151049
ISBN  
9798382840130
DDC  
620.8
저자명  
Mora-Antoinette, Macy.
서명/저자  
The Impact of Acetylcholine Receptors on Osteocytes and Bone Mechanoadaptation
발행사항  
[Sl] : Cornell University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
142 p
주기사항  
Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
주기사항  
Advisor: Lewis, Karl.
학위논문주기  
Thesis (Ph.D.)--Cornell University, 2024.
초록/해제  
요약Bone's ability to adapt to mechanical loads is attributed to the osteocyte. Osteocytes reside embedded in the calcified bone matrix, where they function as the resident tissue mechanotransducer. Calcium (Ca2+) signaling is a key second messenger in osteocyte mechanotransduction, however the details regarding Ca2+ signaling regulation in osteocytes in vivo are not well stratified. The nervous system is known to regulate bone. Osteocytes express components for acetylcholine (ACh) receptors that are known for rapid firing at the neuromuscular junction. Although ACh is known to impact bone mass and fracture risk, the details regarding ACh signaling in bone mechanotransduction remain largely unexplored.This talk identifies osteocytes as a functional target for cholinergic signaling with impacts on bone mechanoadaptation and Ca2+ signaling. We generated osteocyte-targeted conditional knockout mice to remove key components used by ACh receptors. We assessed tissue material make-up, strength, and formations rates to anabolic loading. We also used intravital imaging via two-photon fluorescent microscopy to visualize the Ca2+ dynamics in osteocytes during active mechanical loading of the bone in living mice. Finally, we explore the ability of light-sheet fluorescent microscopy to create high resolution 3D reconstructions of nerve bodies in whole-mount and intact bone specimens. Our results establish a new signaling axis between the brain and bone via the osteocyte with far reaching implications in bone biology which may be vital to treat bone diseases.
일반주제명  
Biomechanics
일반주제명  
Physiology
일반주제명  
Cellular biology
일반주제명  
Neurosciences
키워드  
Bone
키워드  
Calcium signaling
키워드  
Imaging
키워드  
Mechanoadaptation
키워드  
Nicotinic acetylcholine receptors
키워드  
Osteocytes
기타저자  
Cornell University Mechanical Engineering
기본자료저록  
Dissertations Abstracts International. 85-12B.
전자적 위치 및 접속  
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MARC

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■040    ▼aMiAaPQ▼cMiAaPQ
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■1001  ▼aMora-Antoinette,  Macy.▼0(orcid)0009-0001-8412-1891
■24510▼aThe  Impact  of  Acetylcholine  Receptors  on  Osteocytes  and  Bone  Mechanoadaptation
■260    ▼a[Sl]▼bCornell  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a142  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  85-12,  Section:  B.
■500    ▼aAdvisor:  Lewis,  Karl.
■5021  ▼aThesis  (Ph.D.)--Cornell  University,  2024.
■520    ▼aBone's  ability  to  adapt  to  mechanical  loads  is  attributed  to  the  osteocyte.  Osteocytes  reside  embedded  in  the  calcified  bone  matrix,  where  they  function  as  the  resident  tissue  mechanotransducer.  Calcium  (Ca2+)  signaling  is  a  key  second  messenger  in  osteocyte  mechanotransduction,  however  the  details  regarding  Ca2+  signaling  regulation  in  osteocytes  in  vivo  are  not  well  stratified.  The  nervous  system  is  known  to  regulate  bone.  Osteocytes  express  components  for  acetylcholine  (ACh)  receptors  that  are  known  for  rapid  firing  at  the  neuromuscular  junction.  Although  ACh  is  known  to  impact  bone  mass  and  fracture  risk,  the  details  regarding  ACh  signaling  in  bone  mechanotransduction  remain  largely  unexplored.This  talk  identifies  osteocytes  as  a  functional  target  for  cholinergic  signaling  with  impacts  on  bone  mechanoadaptation  and  Ca2+  signaling.  We  generated  osteocyte-targeted  conditional  knockout  mice  to  remove  key  components  used  by  ACh  receptors.  We  assessed  tissue  material  make-up,  strength,  and  formations  rates  to  anabolic  loading.  We  also  used  intravital  imaging  via  two-photon  fluorescent  microscopy  to  visualize  the  Ca2+  dynamics  in  osteocytes  during  active  mechanical  loading  of  the  bone  in  living  mice.  Finally,  we  explore  the  ability  of  light-sheet  fluorescent  microscopy  to  create  high  resolution  3D  reconstructions  of  nerve  bodies  in whole-mount  and  intact  bone  specimens.  Our  results  establish  a  new  signaling  axis  between  the  brain  and  bone  via  the  osteocyte  with  far  reaching  implications  in  bone  biology  which  may  be  vital  to  treat  bone  diseases.
■590    ▼aSchool  code:  0058.
■650  4▼aBiomechanics
■650  4▼aPhysiology
■650  4▼aCellular  biology
■650  4▼aNeurosciences
■653    ▼aBone
■653    ▼aCalcium  signaling
■653    ▼aImaging
■653    ▼aMechanoadaptation
■653    ▼aNicotinic  acetylcholine  receptors
■653    ▼aOsteocytes
■690    ▼a0648
■690    ▼a0379
■690    ▼a0317
■690    ▼a0719
■71020▼aCornell  University▼bMechanical  Engineering.
■7730  ▼tDissertations  Abstracts  International▼g85-12B.
■790    ▼a0058
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160617▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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