Cloning and function of rabbit peroxisome proliferator-activated receptor delta/beta in mature osteoclasts.
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.
Mano
H
H
Department of Oral Anatomy, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-02, Japan.
Kimura
C
C
Fujisawa
Y
Y
Kameda
T
T
Watanabe-Mano
M
M
Kaneko
H
H
Kaneda
T
T
Hakeda
Y
Y
Kumegawa
M
M
D000135:Acid Phosphatase / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001862:Bone Resorption / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000235:genetics; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics; D003001:Cloning, Molecular; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000235:genetics; D007975:Leukotriene B4 / Q000494:pharmacology; D008024:Ligands; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010010:Osteoclasts / Q000378:metabolism*; D020033:Protein Isoforms; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D000071681:Tartrate-Resistant Acid Phosphatase; D013873:Thionucleotides / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D007527:Isoenzymes; D008024:Ligands; D020319:Oligodeoxyribonucleotides, Antisense; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D013873:Thionucleotides; D014157:Transcription Factors; D007975:Leukotriene B4; D011464:Epoprostenol; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002403:Cathepsins; D056657:Cathepsin K; D002256:Carbonic Anhydrases