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2014 ; 93
(11
): 1116-23
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Osteoprotegerin expressed by osteoclasts: an autoregulator of osteoclastogenesis
#MMPMID25256714
Kang JH
; Ko HM
; Moon JS
; Yoo HI
; Jung JY
; Kim MS
; Koh JT
; Kim WJ
; Kim SH
J Dent Res
2014[Nov]; 93
(11
): 1116-23
PMID25256714
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Osteoprotegerin (OPG) is secreted by stromal and osteoblastic lineage cells and
inhibits osteoclastogenesis by preventing the interaction of receptor activator
of nuclear factor-?B ligand (RANKL) with receptor activator of nuclear factor-?B
(RANK). In this study, the expression of OPG in osteoclasts themselves and its
biological functions during osteoclastogenesis were investigated for the first
time. OPG expression in vivo in the developing rat maxilla was examined by
immunofluorescence analysis. OPG expression in osteoclasts during in vitro
osteoclastogenesis was determined by reverse-transcription polymerase
chain-reaction (RT-PCR), Western blot, and immunofluorescence staining. We
determined the function of OPG produced by osteoclasts during osteoclastogenesis
by silencing the OPG gene. The effects of OPG on bone-resorbing activity and
apoptosis of mature osteoclasts were examined by the assay of resorptive pit
formation on calcium-phosphate-coated plate and terminal deoxynucleotidyl
transferase-mediated dUTP nick-end labeling (TUNEL) staining, respectively. In
the immunofluorescence findings, strong immunoreactivities were unexpectedly seen
in multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts
around the growing and erupting tooth germs in the rat alveolar bone. In vitro,
OPG expression was significantly increased during the differentiation of
osteoclasts from mouse bone-marrow-derived cells treated with a combination of
macrophage colony-stimulating factor (M-CSF) and RANKL. Interestingly, it was
found that OPG small interfering (si)RNA treatment during osteoclastogenesis
enhanced the sizes of osteoclasts, but attenuated their bone-resorbing activity.
Also, the increased chromosomal DNA fragmentation and caspase-3 activity in the
late phase of osteoclastogenesis were found to be decreased by treatment with OPG
siRNA. Furthermore, effects of OPG siRNA treatment on osteoclastogenesis and
bone-resorbing activity were recovered by the treatment of exogenous OPG. These
results suggest that OPG, expressed by the osteoclasts themselves, may play an
auto-regulatory role in the late phase of osteoclastogenesis through the
induction of apoptosis.
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