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 patent 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 PEN oil 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 (C) 2009 Elsevier Inc All rights reserved