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J Biol Chem, Vol. 275, Issue 11, 8126-8132, March 17, 2000

Cloning and Function of Rabbit Peroxisome Proliferator-activated Receptor delta /beta in Mature Osteoclasts*

Hiroshi ManoDagger §, Chiharu Kimura, Yukio Fujisawa, Takashi KamedaDagger , Mikiko Watanabe-ManoDagger , Hironori KanekoDagger , Toshio KanedaDagger , Yoshiyuki HakedaDagger , and Masayoshi KumegawaDagger ||

From the Dagger  Department of Oral Anatomy, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-02, Japan, the § Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya, Tokyo 156, Japan, and the  Molecular Pharmacology Laboratory, Pharmaceutical Research Division, Pharmaceutical Group, Takeda Chemical Industries, Ltd., 2-17-85 Juso-Honmachi, Yodogawa, Osaka 532, Japan

Osteoclasts modulate bone resorption under physiological and pathological conditions. Previously, we showed that both estrogens and retinoids regulated osteoclastic bone resorption and postulated that such regulation was directly mediated through their cognate receptors expressed in mature osteoclasts. In this study, we searched for expression of other members of the nuclear hormone receptor superfamily in osteoclasts. Using the low stringency homologous hybridization method, we isolated the peroxisome proliferator-activated receptor delta /beta (PPARdelta /beta ) cDNA from mature rabbit osteoclasts. Northern blot analysis showed that PPARdelta /beta mRNA was highly expressed in highly enriched rabbit osteoclasts. Carbaprostacyclin, a prostacyclin analogue known to be a ligand for PPARdelta /beta , significantly induced both bone-resorbing activities of isolated mature rabbit osteoclasts and mRNA expression of the cathepsin K, carbonic anhydrase type II, and tartrate-resistant acid phosphatase genes in these cells. Moreover, the carbaprostacyclin-induced bone resorption was completely blocked by an antisense phosphothiorate oligodeoxynucleotide of PPARdelta /beta but not by the sense phosphothiorate oligodeoxynucleotide of the same DNA sequence. Our results suggest that PPARdelta /beta may be involved in direct modulation of osteoclastic bone resorption.

* This work was supported in part by a grant from the Ministry of Education, Science, Sports, and Culture of Japan.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence reported in this paper has been submitted to the DDBJ/GenBankTM/EBI Data Bank with accession number AB033614.

|| To whom correspondence should be addressed. Tel.: 81-492-79-2768; Fax: 81-492-71-3523; E-mail: o-anat-1@dent.meikai.ac.jp.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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