Transcriptional activity of nuclei in multinucleated osteoclasts and its modulation by calcitonin

被引:63
作者
Boissy, P
Saltel, F
Bouniol, C
Jurdic, P
Machuca-Gayet, I
机构
[1] Ecole Normale Super Lyon, INRA 913, UMR 5665 CNRS, Lab Biol Mol & Cellulaire, F-69364 Lyon 07, France
[2] INRA Domaine Vilvert, Lab BCM, F-78352 Jouy En Josas, France
关键词
D O I
10.1210/en.143.5.1913
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The function of osteoclasts is to digest the calcified bone matrix. Osteoclasts, together with myotubes, are among the rare examples of multinucleated cells found in higher vertebrates, resulting from the fusion of mononucleated progenitors belonging to the monocyte/macrophage lineage. So far, no information is available about function and transcriptional activity of multiple nuclei in osteoclasts. We have used a run-on technique to visualize RNA synthesis in individual nucleus. We provide the first evidence that nuclei of resorbing osteoclasts, isolated from chick embryo long bones, or differentiated in vitro from murine spleen cells in presence of RANKL and macrophage-colony stimulating factor, are all transcriptionally active. Nevertheless, if transcriptional activity is the same for all the nuclei within a cell, its level varies between osteoclasts: osteoclasts with highly active nuclei are always associated with resorption pits. We found that global transcription activity of resorbing osteoclasts seeded on calcified matrix is down-regulated after 5-h treatment with calcitonin, which transiently blocks resorption. This effect is reversible because calcitonin removal led to nuclear transcription activation. These results indicate a strong correlation between transcription and resorption. Finally, our data indicate that the resorption pit surface is linearly related to the nuclei number per osteoclast, strongly suggesting that functional advantage of osteoclast multinucleation is to improve resorption efficiency.
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页码:1913 / 1921
页数:9
相关论文
共 30 条
[1]  
APLIN JD, 1991, J CELL SCI, V99, P681
[2]   Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor κB (RANK) receptors [J].
Arai, F ;
Miyamoto, T ;
Ohneda, O ;
Inada, T ;
Sudo, T ;
Brasel, K ;
Miyata, T ;
Anderson, DM ;
Suda, T .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (12) :1741-1754
[3]  
BARON R, 1999, PRIMER METABOLIC BON, P3
[4]   Endosperm development [J].
Berger, F .
CURRENT OPINION IN PLANT BIOLOGY, 1999, 2 (01) :28-32
[5]   ENDOGENOUS TRANSCRIPTION OCCURS AT THE 1-CELL STAGE IN THE MOUSE EMBRYO [J].
BOUNIOL, C ;
NGUYEN, E ;
DEBEY, P .
EXPERIMENTAL CELL RESEARCH, 1995, 218 (01) :57-62
[6]   DIFFERENTIAL EXPRESSION OF ACETYLCHOLINE-RECEPTOR MESSENGER-RNA IN NUCLEI OF CULTURED MUSCLE-CELLS [J].
BURSZTAJN, S ;
BERMAN, SA ;
GILBERT, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (08) :2928-2932
[7]   CALCITONIN ALTERS BEHAVIOR OF ISOLATED OSTEOCLASTS [J].
CHAMBERS, TJ ;
MAGNUS, CJ .
JOURNAL OF PATHOLOGY, 1982, 136 (01) :27-39
[8]   ACETYLCHOLINE-RECEPTOR GENE-EXPRESSION AT THE DEVELOPING NEUROMUSCULAR-JUNCTION [J].
DUCLERT, A ;
CHANGEUX, JP .
PHYSIOLOGICAL REVIEWS, 1995, 75 (02) :339-368
[9]  
FALLON MD, 1983, LAB INVEST, V49, P159
[10]  
FOE VE, 1983, J CELL SCI, V61, P31