Enhanced bone regeneration via multimodal actions of synthetic peptide SVVYGLR on osteoprogenitors and osteoclasts.
Recently, the binding sequence Ser-Val-Val-Tyr-Gly-Leu-Arg (SVVYGLR) was found adjacent to the RGD sequence in osteopontin, suggesting involvement in osteo-immune cross-talk. The aim of this study was to investigate bioactive functions of a synthetic SVVYGLR peptide in osteoprogenitor cells and osteoclasts, and to examine potential applications in bone regeneration. The SVVYGLR peptide significantly enhanced the adhesion and proliferation of several human mesenchymal cells including bone marrow-derived mesenchymal stem cells, and alphavbeta3 integrin was involved in cell attachment to the peptide. Additionally, the peptide reduced the number of TRAP-positive multinucleated cells during osteoclastogenesis of RAW264.7 cells and normal murine pre-osteoclasts, and also suppressed NFAT activity and expression of osteoclastogenesis-related mRNAs. When standardized bone defects in rat calvariae were filled with a collagen sponge containing the peptide or PBS (control), the number of TRAP-positive osteoclasts in the grafted sites after 3 weeks was significantly lower in the peptide group. By the 5th week, significantly enhanced resorption of the grafted collagen sponge and new bone formation was observed within and surrounding the sponge in the peptide group. These data suggest that SVVYGLR is an effective bioactive peptide for bone tissue regeneration that promotes attachment and proliferation of osteogenic cells while also suppressing osteoclastogenesis.
Egusa
Hiroshi
H
Department of Fixed Prosthodontics, Division of Oromaxillofacial Regeneration, Osaka University Graduate School of Dentistry, Suita City, Osaka 565-0871, Japan. egu@dent.osaka-u.ac.jp
Kaneda
Yoshitoshi
Y
Akashi
Yoshihiro
Y
Hamada
Yoshinosuke
Y
Matsumoto
Takuya
T
Saeki
Makio
M
Thakor
Devang K
DK
Tabata
Yasuhiko
Y
Matsuura
Nariaki
N
Yatani
Hirofumi
H
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D039302:Integrin alphaVbeta3; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D039302:Integrin alphaVbeta3; D010455:Peptides