Promotion of bone regeneration by CCN2 incorporated into gelatin hydrogel.
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.
Kikuchi
Takeshi
T
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Kubota
Satoshi
S
Asaumi
Koji
K
Kawaki
Harumi
H
Nishida
Takashi
T
Kawata
Kazumi
K
Mitani
Shigeru
S
Tabata
Yasuhiko
Y
Ozaki
Toshifumi
T
Takigawa
Masaharu
M
D000042:Absorption / Q000187:drug effects; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002356:Cartilage / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D004926:Escherichia coli; D005780:Gelatin / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D054457:Tissue Scaffolds
D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D005780:Gelatin; D003094:Collagen