Spatial Distribution of Bax and Bcl‐2 in Osteocytes After Bone Fatigue: Complementary Roles in Bone Remodeling Regulation?

@article{Verborgt2002SpatialDO,
  title={Spatial Distribution of Bax and Bcl‐2 in Osteocytes After Bone Fatigue: Complementary Roles in Bone Remodeling Regulation?},
  author={Olivier Verborgt and Nadine A. Tatton and Robert J. Majeska and Mitchell B. Schaffler},
  journal={Journal of Bone and Mineral Research},
  year={2002},
  volume={17}
}
Osteocyte apoptosis appears to play a key role in the mechanism by which osteoclastic resorption activity targets bone for removal, because osteocyte apoptosis occurs in highly specific association with microdamage and subsequent remodeling after fatigue. However, beyond terminal deoxynucleotidyl transferase (TdT)‐mediated deoxyuridine triphosphate (dUTP)‐biotin nick end labeling (TUNEL) assay, little is known about the mechanisms controlling osteocyte apoptosis in vivo. In the current studies… 
View on Wiley
onlinelibrary.wiley.com
177 Citations
Highly Influential Citations
2
Background Citations
64
Methods Citations
2
Results Citations
3

177 Citations

Citation Type

Citation Type

Activation of resorption in fatigue-loaded bone involves both apoptosis and active pro-osteoclastogenic signaling by distinct osteocyte populations.
TLDR
It is demonstrated that while osteocyte apoptosis triggers the bone remodeling response to microdamage, the neighboring non-apoptotic osteocytes are the major source of pro-osteoclastogenic signals.
Osteocyte Apoptosis Caused by Hindlimb Unloading is Required to Trigger Osteocyte RANKL Production and Subsequent Resorption of Cortical and Trabecular Bone in Mice Femurs
TLDR
Assessment of the spatial and temporal effects of disuse from hindlimb unloading and QVD data indicate that osteocyte apoptosis plays a central and controlling role in triggering osteocyte RANKL production and the activation of new resorption leading to bone loss in disuse.
Osteocyte Apoptosis Controls Activation of Intracortical Resorption in Response to Bone Fatigue
TLDR
It is shown that osteocyte apoptosis is necessary to initiate intracortical bone remodeling in response to fatigue microdamage, a possible dose‐response relationship between the two processes is indicated, and early apoptotic events after fatigue‐induced microdamage may play a substantial role in determining the subsequent course of tissue remodeling is suggested.
Apoptotic osteocytes regulate osteoclast precursor recruitment and differentiation in vitro
TLDR
It is suggested that aOCY directly and indirectly (through atOCY) initiate targeted bone resorption by regulating osteoclast precursor recruitment and differentiation.
Osteocyte apoptosis and control of bone resorption following ovariectomy in mice.
TLDR
It is reported that osteocyte apoptosis is necessary to initiate endocortical remodeling in response to estrogen withdrawal and increases in osteoclastic resorption normally observed after estrogen loss did not occur in OVX mice treated with QVD.
A STUDY OF OSTEOCYTE APOPTOSIS BY REGION AND QUADRANT IN MURINE CORTICAL BONE
TLDR
While the results show that there were no differences among quadrants, regional variations were found in osteocyte apoptosis, a significantly higher density of apoptotic osteocytes was found in the midshaft region which also displayed higher levels of BMP antagonists.
Osteocytes: Sensors of Mechanical Forces and Regulators of Bone Remodeling
Osteocytes make up the largest cell population in bone and are believed to be the main mechanosensory bone cells. During mechanical disuse and overuse, osteocyte viability is compromised and is found…
Quantitative regional associations between remodeling, modeling, and osteocyte apoptosis and density in rabbit tibial midshafts.
TLDR
It was found that osteocyte density and osteocyte lacunar density did not significantly correlate with modeling or remodeling parameters, suggesting that cell viability should be examined in studies correlating bone turnover parameters with the functional role of osteocytes in bone adaptation.
Evidence for the role of osteocytes in the initiation of targeted remodeling.
TLDR
It was demonstrated that damaged osteocytes locally affect osteoclast precursors by secreting osteoclineogenic factors, and thus can have a role in the initiation of resorption in bone remodelling, which strongly supports the idea that damage to osteocyte cellular network has the potential to stimulate osteoclastic proliferation and therefore the activation of Basic Multicellular Units (BMUs).
Osteocyte apoptosis is mechanically regulated and induces angiogenesis in vitro
TLDR
The results suggest that osteocyte apoptosis is flow‐regulated and promotes angiogenesis in a VEGF‐mediated manner.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 72 REFERENCES
Loss of Osteocyte Integrity in Association with Microdamage and Bone Remodeling After Fatigue In Vivo
  • O. Verborgt, G. Gibson, M. Schaffler
  • Chemistry, Medicine
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 2000
TLDR
The studies show that osteocyte apoptosis is induced by bone fatigue, this apoptotic activity is localized to regions of bone that contain microcracks, and osteoclastic resorption after fatigue also coincides with regions of osteocytes apoptosis.
DNA fragmentation during bone formation in neonatal rodents assessed by transferase‐mediated end labeling
  • A. Bronckers, W. Goei, +4 authors E. Burger
  • Biology, Medicine
    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
  • 1996
TLDR
It is concluded that some of the osteocytes in deeper layers of bone die within their lacuna and disperse nuclear fragments over the extracellular matrix, and that during endochondral ossification, substantial numbers of late hypertrophic chondrocyte cells undergo cell death.
Identification of apoptotic changes in osteocytes in normal and pathological human bone.
TLDR
It was found that the distribution of potentially apoptotic cells in the infant and pathological bone was anatomically nonuniform, raising the intriguing possibility of a functional relationship between bone turnover and the controlled cell death of osteocytes.
Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone.
TLDR
Evidence is provided that glucocorticoid-induced bone disease arises from changes in the numbers of bone cells, whereas decreased production and apoptosis of osteoblasts would account for the decline in bone formation and trabecular width.
The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone.
TLDR
GnRH-a therapy caused a higher prevalence of dead osteocytes in iliac bone, probably caused by the increase in the observed proportion of osteocytes showing apoptotic changes, revealing a possible mechanism whereby estrogen deficiency could lead to increased bone fragility with or without an accompanying net bone loss.
The Immunohistochemical Localization of Fas and Fas Ligand in Jaw Bone and Tooth Germ of Human Fetuses
TLDR
Findings indicated that Fas-mediated apoptosis was inhibited by the Bcl-2 family in the development of teeth.
Expression of Bcl-2 protein in the epiphyseal plate cartilage and trabecular bone of growing rats
TLDR
Data indicate that Bcl-2 helps maintain chondrocytes and osteoblasts until their terminal maturation, as well as inhibiting the action of the apoptosis-inducer, Bax, which indicates that it protects against cell death.
Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip.
TLDR
Results indicate that glucocorticoid-induced osteonecrosis is a misnomer, and osteocyte apoptosis, a cumulative and irreparable defect, could uniquely disrupt the mechanosensory function of the osteocyte network and thus start the inexorable sequence of events leading to collapse of the femoral head.
Bcl‐2, tissue transglutaminase and p53 protein expression in the apoptotic cascade in ribs of premature infants
TLDR
Findings would indicate that human growth plate chondrocytes appear to show little provision for ensuring cell longevity, and osteocyte apoptosis appears negatively correlated with the skeletal distribution of Bcl‐2 protein in the human infant, implying a potential selective vulnerability in individual cells.
Differential expression of the protooncogene bcl-2 in normal and osteoarthritic human articular cartilage.
TLDR
The results show that bcl-2 is expressed in healthy adult and osteoarthritic human cartilage and the increased staining of chondrocytes adjacent to osteoartritic defects indicates a differential regulation of programmed cell death during the degenerative process in OA.
...
1
2
3
4
5
...