PEDF regulates osteoclasts via osteoprotegerin and RANKL

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Akiyama, Toru, Dass, Crispin R, Shinoda, Yusuke, Kawano, Hirotaka, Tanaka, Sakae and Choong, Peter F. M (2010) PEDF regulates osteoclasts via osteoprotegerin and RANKL. Biochemical and Biophysical Research Communications, 391 (1). pp. 789-794. ISSN 0006-291X (print) 1090-2104 (online)

Abstract

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.

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Item type Article
URI https://vuir.vu.edu.au/id/eprint/7575
DOI https://doi.org/10.1016/j.bbrc.2009.11.139
Official URL http://www.sciencedirect.com/science/article/pii/S...
Subjects Historical > Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
Historical > FOR Classification > 0304 Medicinal and Bimolecular Chemistry
Historical > FOR Classification > 1112 Oncology and Carcinogenesis
Historical > SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Keywords ResPubID21871. PEDF, osteoclast, RANK, RANKL, OPG
Citations in Scopus 53 - View on Scopus
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