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Regulation of osteoclastogenesis by gap junction communication.
- Source :
-
Journal of cellular biochemistry [J Cell Biochem] 2006 Oct 01; Vol. 99 (2), pp. 528-37. - Publication Year :
- 2006
-
Abstract
- Receptor activator of NF-kappaB ligand (RANKL) is crucial in osteoclastogenesis but signaling events involved in osteoclast differentiation are far from complete and other signals may play a role in osteoclastogenesis. A more direct pathway for cellular crosstalk is provided by gap junction intercellular channel, which allows adjacent cells to exchange second messengers, ions, and cellular metabolites. Here we have investigated the role of gap junction communication in osteoclastogenesis in mouse bone marrow cultures. Immunoreactive sites for the gap junction protein connexin 43 (Cx43) were detected in the marrow stromal cells and in mature osteoclasts. Carbenoxolone (CBX) functionally blocked gap junction communication as demonstrated by a scrape loading Lucifer Yellow dye transfer technique. CBX caused a dose-dependent inhibition (significant > or = 90 microM) of the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells formed in 7- to 8-day marrow cultures stimulated by parathyroid hormone (PTH; 10 nM) or forskolin (FSK; 1 microM). Furthermore, CBX (100 microM) significantly inhibited prostaglandin E2 (PGE2; 10 microM) and 1,25(OH)2-vitamin D3 stimulated osteoclast differentiation in the mouse bone marrow cultures. Consequently, quantitative real-time polymerase chain reaction (PCR) analysis demonstrated that CBX downregulated the expression of osteoclast phenotypic markers, but without having any significant effects on RANK, RANKL, and osteoprotegerin (OPG) mRNA expression. However, the results demonstrated that CBX significantly inhibits RANKL-stimulated (100 ng/ml) osteoclastogenesis in the mouse bone marrow cultures. Taken together, our results suggests that gap junctional diffusion of messenger molecules interacts with signaling pathways downstream RANKL in osteoclast differentiation. Further studies are required to define the precise mechanisms and molecular targets involved.<br /> (Copyright 2006 Wiley-Liss, Inc.)
- Subjects :
- Animals
Base Sequence
Bone Resorption metabolism
Calcitriol pharmacology
Carbenoxolone pharmacology
Carrier Proteins genetics
Carrier Proteins metabolism
Cell Communication drug effects
Cell Differentiation drug effects
Cells, Cultured
Colforsin pharmacology
Connexin 43 genetics
Connexin 43 metabolism
DNA, Complementary genetics
Dinoprostone pharmacology
Gap Junctions drug effects
Glycoproteins genetics
Membrane Glycoproteins genetics
Membrane Glycoproteins metabolism
Mice
Osteoclasts cytology
Osteoclasts drug effects
Osteoprotegerin
Parathyroid Hormone pharmacology
RANK Ligand
RNA, Messenger genetics
RNA, Messenger metabolism
Receptor Activator of Nuclear Factor-kappa B
Receptors, Cytoplasmic and Nuclear genetics
Receptors, Tumor Necrosis Factor genetics
Signal Transduction drug effects
Gap Junctions metabolism
Osteoclasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0730-2312
- Volume :
- 99
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of cellular biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 16639710
- Full Text :
- https://doi.org/10.1002/jcb.20866