TY - JOUR
T1 - CCN2 enhances RANKL-induced osteoclast differentiation via direct binding to RANK and OPG
AU - Aoyama, Eriko
AU - Kubota, Satoshi
AU - Khattab, Hany Mohamed
AU - Nishida, Takashi
AU - Takigawa, Masaharu
N1 - Funding Information:
We thank Dr. Takako Hattori and Dr. Harumi Kawaki for their helpful suggestions and Ms. Eri Yashiro and Yoshiko Miyake for their secretarial assistance. This study was supported in part by the programs JSPS KAKENHI Grants-in-aid for Young Scientists (B), No. 25861755 (to EA) and JSPS KAKENHI Grants-in-aid for Scientific Research (S), No. 19109008 (to MT) and (B), No. 24390415 (to MT) and (C), No. 26462810 (to TN), and (C), No. 25462886 (to SK), and by JSPS KAKENHI Challenging Exploratory Research , No. 266708 (to MT).
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a multi-potent factor for mesenchymal cells such as chondrocytes, osteoblasts, osteoclasts, and endothelial cells. CCN2 is also known as a modulator of other cytokines and receptors via direct molecular interactions with them. We screened additional factors binding to CCN2 and found receptor activator of NF-kappa B (RANK) as one of them. RANK is also known as TNF-related activation-induced cytokine (TRANCE) receptor, and its signaling plays a critical role in osteoclastogenesis. Notable affinity between CCN2 and RANK was confirmed by using surface plasmon resonance (SPR) analysis. In fact, CCN2 enhanced the RANK-mediated signaling, such as occurs in NF-kappa B, p38 and JNK pathways, in pre-osteoclastic RAW264.7 cells; whereas CCN2 had no influence on RANK-RANK ligand (RANKL) binding. Moreover, CCN2 also significantly bound to osteoprotegerin (OPG), which is a decoy receptor of RANKL. Of note, OPG markedly inhibited the binding between CCN2 and RANK; and CCN2 canceled the inhibitory effect of OPG on osteoclast differentiation. These findings suggest CCN2 as a candidate of the fourth factor in the RANK/RANKL/OPG system for osteoclastogenesis, which regulates OPG and RANK via direct interaction.
AB - CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a multi-potent factor for mesenchymal cells such as chondrocytes, osteoblasts, osteoclasts, and endothelial cells. CCN2 is also known as a modulator of other cytokines and receptors via direct molecular interactions with them. We screened additional factors binding to CCN2 and found receptor activator of NF-kappa B (RANK) as one of them. RANK is also known as TNF-related activation-induced cytokine (TRANCE) receptor, and its signaling plays a critical role in osteoclastogenesis. Notable affinity between CCN2 and RANK was confirmed by using surface plasmon resonance (SPR) analysis. In fact, CCN2 enhanced the RANK-mediated signaling, such as occurs in NF-kappa B, p38 and JNK pathways, in pre-osteoclastic RAW264.7 cells; whereas CCN2 had no influence on RANK-RANK ligand (RANKL) binding. Moreover, CCN2 also significantly bound to osteoprotegerin (OPG), which is a decoy receptor of RANKL. Of note, OPG markedly inhibited the binding between CCN2 and RANK; and CCN2 canceled the inhibitory effect of OPG on osteoclast differentiation. These findings suggest CCN2 as a candidate of the fourth factor in the RANK/RANKL/OPG system for osteoclastogenesis, which regulates OPG and RANK via direct interaction.
KW - CCN2 family protein 2 (CCN2)
KW - Osteoclast
KW - Osteoprotegerin (OPG)
KW - RANK ligand (RANKL)
KW - Receptor activator of nuclear factor-κB ligand (RANK)
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U2 - 10.1016/j.bone.2014.12.058
DO - 10.1016/j.bone.2014.12.058
M3 - Article
C2 - 25554597
AN - SCOPUS:84922523169
SN - 8756-3282
VL - 73
SP - 242
EP - 248
JO - Bone
JF - Bone
ER -
