Promotion by collagen tripeptide of type I collagen gene expression in human osteoblastic cells and fracture healing of rat femur.
Peptides produced by the enzymatic degradation of collagens are reported to have various activities of biological and medical interest. The mechanisms underlying their actions are, however, poorly understood. We have produced, by collagenase digestion of type I collagen, a highly purified, non-antigenic, and low allergenic tripeptide fraction (collagen tripeptide, Ctp). We report here the effects of Ctp on the in vivo bone fracture healing and in vitro calcification of osteoblastic cells. An oral administration of Ctp to rats with a femur fracture accelerated the fracture healing. Ctp apparently stimulated the calcification of human osteoblastic cells in culture. This osteotrophic effect was accompanied by a significant increase in type I collagen protein production and its mRNA levels. DNA microarray and quantitative RT-PCR analyses demonstrated that Ctp upregulated the bone-specific transcription factor, Osterix, suggesting that the induction of type I collagen gene expression by Ctp was mediated by upregulation of this factor.
Tsuruoka
Naoki
N
Department of Biochemistry, Kanazawa Medical University School of Medicine, Ishikawa 920-0293, Japan. tsuruoka@kanazawa-med.ac.jp
Yamato
Rumiko
R
Sakai
Yasuo
Y
Yoshitake
Yoshino
Y
Yonekura
Hideto
H
D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects; D024042:Collagen Type I / Q000032:analysis / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D005264:Femoral Fractures / Q000378:metabolism*; D017102:Fracture Healing / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D015854:Up-Regulation
D024042:Collagen Type I; D012333:RNA, Messenger; C526216:collagen tripeptide Ctp, human