TY - JOUR
T1 - PEDF regulates osteoclasts via osteoprotegerin and RANKL
AU - Akiyama, Toru
AU - Dass, Crispin R.
AU - Shinoda, Yusuke
AU - Kawano, Hirotaka
AU - Tanaka, Sakae
AU - Choong, Peter F.M.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Bone homeostasis is maintained through a balance between bone formation and resorption. Bone resorption is mainly carried out by a specific type of cell called the osteoclast (OCL). Previously, expression of pigment epithelium-derived factor (PEDF), the most potent endogenous inhibitor of angiogenesis, has been demonstrated in bone tissue and it known to induce differentiation in osteoblastic cells. Furthermore, therapeutic effects of PEDF on osteosarcoma, a prevalent primary bone tumor, with inhibition of bone destruction has been shown. Thus, PEDF is possibly involved in bone homeostasis as an inhibitor of bone resorption. To address this involvement, we studied the effect of PEDF on OCL function. OCL differentiation, RANKL-mediated survival and bone resorption activity were inhibited by PEDF in a dose-dependent manner. PEDF upregulated osteoprotegerin (OPG), which naturally blocks OCL maturation, in primary osteoblasts and OCL precursor cells. These results suggest that PEDF inhibits OCL function via regulating OPG expression, and thereby contributes to the maintenance of bone homeostasis.
AB - Bone homeostasis is maintained through a balance between bone formation and resorption. Bone resorption is mainly carried out by a specific type of cell called the osteoclast (OCL). Previously, expression of pigment epithelium-derived factor (PEDF), the most potent endogenous inhibitor of angiogenesis, has been demonstrated in bone tissue and it known to induce differentiation in osteoblastic cells. Furthermore, therapeutic effects of PEDF on osteosarcoma, a prevalent primary bone tumor, with inhibition of bone destruction has been shown. Thus, PEDF is possibly involved in bone homeostasis as an inhibitor of bone resorption. To address this involvement, we studied the effect of PEDF on OCL function. OCL differentiation, RANKL-mediated survival and bone resorption activity were inhibited by PEDF in a dose-dependent manner. PEDF upregulated osteoprotegerin (OPG), which naturally blocks OCL maturation, in primary osteoblasts and OCL precursor cells. These results suggest that PEDF inhibits OCL function via regulating OPG expression, and thereby contributes to the maintenance of bone homeostasis.
KW - OPG
KW - Osteoclast
KW - PEDF
KW - RANK
KW - RANKL
UR - http://www.scopus.com/inward/record.url?scp=72949093334&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2009.11.139
DO - 10.1016/j.bbrc.2009.11.139
M3 - 記事
C2 - 19945427
AN - SCOPUS:72949093334
SN - 0006-291X
VL - 391
SP - 789
EP - 794
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -