PEDF regulates osteoclasts via osteoprotegerin and RANKL.
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.
Akiyama
Toru
T
Departments of Orthopaedics and Surgery, University of Melbourne, St Vincent's Health, Melbourne, Australia.
Dass
Crispin R
CR
Shinoda
Yusuke
Y
Kawano
Hirotaka
H
Tanaka
Sakae
S
Choong
Peter F M
PF
D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D005136:Eye Proteins / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D010010:Osteoclasts / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D053244:Osteoprotegerin / Q000096:biosynthesis*; D053245:RANK Ligand / Q000096:biosynthesis*; D015843:Serpins / Q000494:pharmacology / Q000502:physiology*; D000099174:Pigment Epithelium-Derived Factor
D005136:Eye Proteins; D009414:Nerve Growth Factors; D053244:Osteoprotegerin; D053245:RANK Ligand; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor