Abstract
CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a unique molecule that promotes the entire endochondral ossification process and regeneration of damaged articular cartilage. Also, CCN2 has been shown to enhance the adhesion and migration of bone marrow stromal cells as well as the growth and differentiation of osteoblasts; hence, its utility in bone regeneration has been suggested. Here, we evaluated the effect of CCN2 on the regeneration of an intractable bone defect in a rat model. First, we prepared two recombinant CCN2s of different origins, and the one showing the stronger effect on osteoblasts in vitro was selected for further evaluation, based on the result of an in vitro bioassay. Next, to obtain a sustained effect, the recombinant CCN2 was incorporated into gelatin hydrogel that enabled the gradual release of the factor. Evaluation in vivo indicated that CCN2 continued to be released at least for up to 14 days after its incorporation. Application of the gelatin hydrogel-CCN2 complex, together with a collagen scaffold to the bone defect prepared in a rat femur resulted in remarkable induction of osteoblastic mineralization markers within 2 weeks. Finally, distinct enhancement of bone regeneration was observed 3 weeks after the application of the complex. These results confirm the utility of CCN2 in the regeneration of intractable bone defects in vivo when the factor is incorporated into gelatin hydrogel.
| Original language | English |
|---|---|
| Pages (from-to) | 1089-1098 |
| Number of pages | 10 |
| Journal | Tissue Engineering - Part A |
| Volume | 14 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2008 |
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ASJC Scopus subject areas
- Bioengineering
- Biochemistry
- Biomedical Engineering
- Biomaterials
Cite this
Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel. / Kikuchi, Takeshi; Kubota, Satoshi; Asaumi, Koji; Kawaki, Harumi; Nishida, Takashi; Kawata, Kazumi; Mitani, Shigeru; Tabata, Yasuhiko; Ozaki, Toshihumi; Takigawa, Masaharu.
In: Tissue Engineering - Part A, Vol. 14, No. 6, 01.06.2008, p. 1089-1098.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel
AU - Kikuchi, Takeshi
AU - Kubota, Satoshi
AU - Asaumi, Koji
AU - Kawaki, Harumi
AU - Nishida, Takashi
AU - Kawata, Kazumi
AU - Mitani, Shigeru
AU - Tabata, Yasuhiko
AU - Ozaki, Toshihumi
AU - Takigawa, Masaharu
PY - 2008/6/1
Y1 - 2008/6/1
N2 - CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a unique molecule that promotes the entire endochondral ossification process and regeneration of damaged articular cartilage. Also, CCN2 has been shown to enhance the adhesion and migration of bone marrow stromal cells as well as the growth and differentiation of osteoblasts; hence, its utility in bone regeneration has been suggested. Here, we evaluated the effect of CCN2 on the regeneration of an intractable bone defect in a rat model. First, we prepared two recombinant CCN2s of different origins, and the one showing the stronger effect on osteoblasts in vitro was selected for further evaluation, based on the result of an in vitro bioassay. Next, to obtain a sustained effect, the recombinant CCN2 was incorporated into gelatin hydrogel that enabled the gradual release of the factor. Evaluation in vivo indicated that CCN2 continued to be released at least for up to 14 days after its incorporation. Application of the gelatin hydrogel-CCN2 complex, together with a collagen scaffold to the bone defect prepared in a rat femur resulted in remarkable induction of osteoblastic mineralization markers within 2 weeks. Finally, distinct enhancement of bone regeneration was observed 3 weeks after the application of the complex. These results confirm the utility of CCN2 in the regeneration of intractable bone defects in vivo when the factor is incorporated into gelatin hydrogel.
AB - CCN family protein 2/connective tissue growth factor (CCN2/CTGF) is a unique molecule that promotes the entire endochondral ossification process and regeneration of damaged articular cartilage. Also, CCN2 has been shown to enhance the adhesion and migration of bone marrow stromal cells as well as the growth and differentiation of osteoblasts; hence, its utility in bone regeneration has been suggested. Here, we evaluated the effect of CCN2 on the regeneration of an intractable bone defect in a rat model. First, we prepared two recombinant CCN2s of different origins, and the one showing the stronger effect on osteoblasts in vitro was selected for further evaluation, based on the result of an in vitro bioassay. Next, to obtain a sustained effect, the recombinant CCN2 was incorporated into gelatin hydrogel that enabled the gradual release of the factor. Evaluation in vivo indicated that CCN2 continued to be released at least for up to 14 days after its incorporation. Application of the gelatin hydrogel-CCN2 complex, together with a collagen scaffold to the bone defect prepared in a rat femur resulted in remarkable induction of osteoblastic mineralization markers within 2 weeks. Finally, distinct enhancement of bone regeneration was observed 3 weeks after the application of the complex. These results confirm the utility of CCN2 in the regeneration of intractable bone defects in vivo when the factor is incorporated into gelatin hydrogel.
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UR - http://www.scopus.com/inward/citedby.url?scp=45549107295&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2007.0167
DO - 10.1089/ten.tea.2007.0167
M3 - Article
C2 - 19230129
AN - SCOPUS:45549107295
VL - 14
SP - 1089
EP - 1098
JO - Tissue Engineering - Part A.
JF - Tissue Engineering - Part A.
SN - 1937-3341
IS - 6
ER -