Dermatan sulfate inhibits osteoclast formation by binding to receptor activator of NF-kappa B ligand.
Dermatan sulfate (DS) is a major component of extracellular matrices in mammalian tissues. In the present study, DS demonstrated a high level of binding activity to receptor activator of NF-kappaB ligand (RANKL) and obstructed the binding of RANK to RANKL, determined using a quartz-crystal microbalance (QCM) technique. Further, when mouse bone marrow cells were cultured with RANKL and macrophage colony-stimulating factor, DS suppressed tartrate-resistant acid phosphatase-positive multinucleated cell formation in a dose-dependent manner. In addition, immunoblot analyses revealed that DS reduced the levels of phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase protein in mouse osteoclast progenitor cells stimulated with RANKL. Together, these results indicate that DS regulates osteoclast formation through binding to RANKL and inhibition of signal transduction in osteoclast progenitor cells, suggesting that it has an important role in bone metabolism in pathological conditions.
Shinmyouzu
Kouhei
K
Division of Oral and Maxillofacial Reconstructive Surgery, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580, Japan.
Takahashi
Tetsu
T
Ariyoshi
Wataru
W
Ichimiya
Hisashi
H
Kanzaki
Shin
S
Nishihara
Tatsuji
T
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D003871:Dermatan Sulfate / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006131:Growth Inhibitors / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology*; D011485:Protein Binding / Q000502:physiology; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism
D006131:Growth Inhibitors; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D003871:Dermatan Sulfate