TY - JOUR
T1 - Differential roles of CCN family proteins during osteoblast differentiation
T2 - Involvement of Smad and MAPK signaling pathways
AU - Kawaki, Harumi
AU - Kubota, Satoshi
AU - Suzuki, Akiko
AU - Suzuki, Makoto
AU - Kohsaka, Kumiko
AU - Hoshi, Kenji
AU - Fujii, Toshiya
AU - Lazar, Noureddine
AU - Ohgawara, Toshihiro
AU - Maeda, Takeyasu
AU - Perbal, Bernard
AU - Takano-Yamamoto, Teruko
AU - Takigawa, Masaharu
N1 - Funding Information:
This work was supported by grants from the programs Grants-in-Aid for Scientific Research (S) [to M.T.; No. 19109008 ], (A) [to T. T-Y.; No. 20249081 ], (C) [to S.K.; No. 21592360 ], Grants-in-Aid for Exploratory Research [to M.T.; No. 19659487 ], Grants-in-Aid for Research Activity Start-up [to H. K.; No. 20890024 ] from Japan Society for the Promotion of Science (JSPS), and by a grant from the Foundation of Sanyo Broadcasting (to S.K.). The work performed in Prof. Perbal's laboratory was supported by the French Ministry of Education and Research and by European Union (Prothets grant; contract number LSHC-CT-2004-5030306 ).
PY - 2011/11
Y1 - 2011/11
N2 - CCN family proteins play diverse roles in many aspects of cellular processes such as proliferation, differentiation, adhesion, migration, angiogenesis and survival. In the bone tissue of vertebrate species, the expression of most CCN family members has been observed in osteoblasts. However, their spatial and temporal distributions, as well as their functions, are still only partially understood. In this study, we evaluated the localization of CCN family members in skeletal tissue in vivo and comparatively analyzed the gene expression patterns and functions of the members in murine osteoblasts in primary culture. Immunofluorescent analyses revealed that the CCN family members were differentially produced in osteoblasts and osteocytes. The presence of all Ccn transcripts was confirmed in those osteoblasts. Among the members, CCN1, CCN2, CCN4 and CCN5 were found in osteocytes. CCN4 and CCN5 were distributed in osteocytes located inside of bone matrix as well. Next, we investigated the expression pattern of Ccn family members during osteoblast differentiation. Along with differentiation, most of the members followed proper gene expression patterns; whereas, Ccn4 and Ccn5 showed quite similar patterns. Furthermore, we evaluated the effects of CCN family members on the osteoblastic activities by using recombinant CCN proteins and RNA interference method. Five members of this family displayed positive effects on osteoblast proliferation or differentiation. Of note, CCN3 drastically inhibited the osteoblast activities. Each Ccn specific siRNA could modulate osteoblast activities in a manner expected by the observed effect of respective recombinant CCN protein. In addition, we found that extracellular signal-regulated kinase1/2 and p38 mitogen-activated protein kinase pathways were critically involved in the CCN family member-mediated modification of osteoblast activities. Collectively, all Ccn family members were found to be differentially expressed along with differentiation and therefore could participate in progression of the osteoblast lineage.
AB - CCN family proteins play diverse roles in many aspects of cellular processes such as proliferation, differentiation, adhesion, migration, angiogenesis and survival. In the bone tissue of vertebrate species, the expression of most CCN family members has been observed in osteoblasts. However, their spatial and temporal distributions, as well as their functions, are still only partially understood. In this study, we evaluated the localization of CCN family members in skeletal tissue in vivo and comparatively analyzed the gene expression patterns and functions of the members in murine osteoblasts in primary culture. Immunofluorescent analyses revealed that the CCN family members were differentially produced in osteoblasts and osteocytes. The presence of all Ccn transcripts was confirmed in those osteoblasts. Among the members, CCN1, CCN2, CCN4 and CCN5 were found in osteocytes. CCN4 and CCN5 were distributed in osteocytes located inside of bone matrix as well. Next, we investigated the expression pattern of Ccn family members during osteoblast differentiation. Along with differentiation, most of the members followed proper gene expression patterns; whereas, Ccn4 and Ccn5 showed quite similar patterns. Furthermore, we evaluated the effects of CCN family members on the osteoblastic activities by using recombinant CCN proteins and RNA interference method. Five members of this family displayed positive effects on osteoblast proliferation or differentiation. Of note, CCN3 drastically inhibited the osteoblast activities. Each Ccn specific siRNA could modulate osteoblast activities in a manner expected by the observed effect of respective recombinant CCN protein. In addition, we found that extracellular signal-regulated kinase1/2 and p38 mitogen-activated protein kinase pathways were critically involved in the CCN family member-mediated modification of osteoblast activities. Collectively, all Ccn family members were found to be differentially expressed along with differentiation and therefore could participate in progression of the osteoblast lineage.
KW - CCN family
KW - Differentiation
KW - ERK1/2
KW - Osteoblast
KW - Osteocyte
KW - P38MAPK
KW - Signaling molecules
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UR - http://www.scopus.com/inward/citedby.url?scp=80054831375&partnerID=8YFLogxK
U2 - 10.1016/j.bone.2011.06.033
DO - 10.1016/j.bone.2011.06.033
M3 - Article
C2 - 21763478
AN - SCOPUS:80054831375
SN - 8756-3282
VL - 49
SP - 975
EP - 989
JO - Bone
JF - Bone
IS - 5
ER -
