PMID- 19925896
OWN - NLM
STAT- MEDLINE
DCOM- 20100920
LR  - 20211020
IS  - 1873-2763 (Electronic)
IS  - 8756-3282 (Print)
IS  - 1873-2763 (Linking)
VI  - 46
IP  - 3
DP  - 2010 Mar
TI  - Osteocyte apoptosis and control of bone resorption following ovariectomy in mice.
PG  - 577-83
LID - 10.1016/j.bone.2009.11.006 [doi]
AB  - INTRODUCTION: Osteocyte apoptosis has been linked to bone resorption resulting 
      from estrogen depletion and other resorptive stimuli; however, precise spatial 
      and temporal relationships between the two events have not been clearly 
      established. The purpose of this study was to characterize the patterns of 
      osteocyte apoptosis in relation to bone resorption following ovariectomy to test 
      whether osteocyte apoptosis occurs preferentially in areas known to activate 
      resorption. Moreover, we report that osteocyte apoptosis is necessary to initiate 
      endocortical remodeling in response to estrogen withdrawal. MATERIALS AND 
      METHODS: Adult female C57BL/6J mice (17 weeks old) underwent either bilateral 
      ovariectomy (OVX), or sham surgery (SHAM) and were euthanized on days 3, 7, 14, 
      or 21 days after OVX. Diaphyseal cross-sections were stained by 
      immunohistochemistry for activated caspase-3 as a marker of apoptosis. The 
      percentages of caspase-positive stained osteocytes (Casp+Ot.) were measured along 
      major and minor anatomical axes around the femoral diaphysis to evaluate the 
      distribution of osteocyte apoptosis after estrogen loss; resorption surface was 
      measured at the adjacent endocortical regions. In a second study to test whether 
      osteocyte apoptosis plays a regulatory role in the initiation of bone resorption, 
      a group of OVX mice received the pan-caspase inhibitor, QVDOPh, to inhibit 
      osteocyte apoptosis. Remaining experimental and sham groups received either QVD 
      or Vehicle. RESULTS: OVX increased osteocyte apoptosis in a non-uniform 
      distribution throughout the femoral diaphyses. Increases in Casp+osteocytes were 
      predominantly located in the posterior diaphyseal cortex. Here, the number of 
      apoptotic osteocytes 4- to 7-fold higher than sham controls (p<0.005) by day 3 
      post-OVX and remained elevated. Increases in resorption post-OVX also occurred 
      along the posterior endocortical surface overlying the region of osteocyte 
      apoptosis, but these increases occurred only at 14 and 21 days post-OVX (p<0.002) 
      well after the increases in osteocyte apoptosis. Treatment with QVD in OVX 
      animals suppressed osteocyte apoptosis, with levels in QVD-treated samples 
      equivalent to baseline. Moreover, the increases in osteoclastic resorption 
      normally observed after estrogen loss did not occur in OVX mice treated with QVD. 
      CONCLUSIONS: The results of this study demonstrate that osteocyte apoptosis 
      following estrogen loss occur regionally, rather than uniformly throughout the 
      cortex. We also showed that estrogen loss increased osteocyte apoptosis. 
      Apoptotic osteocytes were overwhelmingly localized within the posterior cortical 
      region, the location where endocortical resorption was subsequently activated in 
      ovariectomized mice. Finally, the increases in osteoclastic resorption normally 
      observed after estrogen withdrawal did not occur in the absence of osteocyte 
      apoptosis indicating that this apoptosis is necessary to activate endocortical 
      remodeling following estrogen loss.
FAU - Emerton, K B
AU  - Emerton KB
AD  - Department of Biomedical Engineering, The City College of New York, USA.
FAU - Hu, B
AU  - Hu B
FAU - Woo, A A
AU  - Woo AA
FAU - Sinofsky, A
AU  - Sinofsky A
FAU - Hernandez, C
AU  - Hernandez C
FAU - Majeska, R J
AU  - Majeska RJ
FAU - Jepsen, K J
AU  - Jepsen KJ
FAU - Schaffler, M B
AU  - Schaffler MB
LA  - eng
GR  - AR44927/AR/NIAMS NIH HHS/United States
GR  - AR41210/AR/NIAMS NIH HHS/United States
GR  - R29 AR044927/AR/NIAMS NIH HHS/United States
GR  - R01 AR041210-17/AR/NIAMS NIH HHS/United States
GR  - R01 AR041210/AR/NIAMS NIH HHS/United States
GR  - R56 AR044927/AR/NIAMS NIH HHS/United States
GR  - R01 AR044927/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20091117
PL  - United States
TA  - Bone
JT  - Bone
JID - 8504048
SB  - IM
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Bone Resorption/metabolism/*pathology/physiopathology
MH  - Female
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteocytes/metabolism/*pathology/physiology
MH  - *Ovariectomy/adverse effects
MH  - Time Factors
PMC - PMC2824001
MID - NIHMS161773
COIS- Conflict of Interest Statement: None of the authors has a conflict of interest
EDAT- 2009/11/21 06:00
MHDA- 2010/09/21 06:00
PMCR- 2011/03/01
CRDT- 2009/11/21 06:00
PHST- 2009/07/20 00:00 [received]
PHST- 2009/10/22 00:00 [revised]
PHST- 2009/11/06 00:00 [accepted]
PHST- 2009/11/21 06:00 [entrez]
PHST- 2009/11/21 06:00 [pubmed]
PHST- 2010/09/21 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - S8756-3282(09)02018-3 [pii]
AID - 10.1016/j.bone.2009.11.006 [doi]
PST - ppublish
SO  - Bone. 2010 Mar;46(3):577-83. doi: 10.1016/j.bone.2009.11.006. Epub 2009 Nov 17.