title: Chronological histological changes during bone regeneration on a non-crosslinked atelocollagen matrix.
abstract: Cleavage of the antigenic telopeptide region from type I collagen yields atelocollagen, and this is widely used as a scaffold for bone regeneration combined with cells, growth factors, etc. However, neither the biological effect of atelocollagen alone or its contribution to bone regeneration has been well studied. We evaluated the chronological histological changes during bone regeneration following implantation of non-crosslinked atelocollagen (Koken Co., Ltd.) in rat calvarial defects. One week after implantation,  osteogenic cells positive for runt-related transcription factor 2 (Runx2) and osteoclasts positive for tartrate-resistant acid phosphatase (TRAP) were present in the atelocollagen implant in the absence of bone formation. The number of Runx2-positive osteogenic cells and Osterix-positive osteoblasts increased 2 weeks after implantation, and bone matrix proteins (osteopontin, OPN; osteocalcin, OC; dentin matrix protein 1, DMP1) were distributed in newly formed bone in a way comparable to normal bone. Some resorption cavities containing osteoclasts were also present. By 3 weeks after implantation, most of the implanted atelocollagen was replaced by new bone containing many resorption cavities, and OPN, OC, and DMP1 were deposited in the residual collagenous matrix. After 4 weeks, nearly all of the atelocollagen implant was replaced with new bone including hematopoietic marrow. Immunohistochemistry for the telopeptide region of type I collagen (TeloCOL1) during these processes demonstrated that the TeloCOL1-negative atelocollagen implant was replaced by TeloCOL1-positive collagenous matrix and new bone, indicating that new bone was mostly composed of endogenous type I collagen. These findings suggest that the atelocollagen itself can support bone regeneration by promoting osteoblast differentiation and type I collagen production.
authors.affiliation: Department of Oral Pathology, Osaka University Graduate School of Dentistry, Yamadaoka, Suita, Osaka, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kagawa
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Kishino
authors.forename: Sunao
authors.initials: S
authors.lastname: Sato
authors.forename: Ken
authors.initials: K
authors.lastname: Ishida
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ikebe
authors.forename: Kaori
authors.initials: K
authors.lastname: Oya
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishimoto
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nakano
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.forename: Satoru
authors.initials: S
authors.lastname: Toyosawa
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D018786:Bone Substitutes / Q000627:therapeutic use*; D003094:Collagen / Q000627:therapeutic use*; D024042:Collagen Type I / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010012:Osteogenesis; D051381:Rats; D017208:Rats, Wistar; D012886:Skull / Q000033:anatomy & histology*; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D018786:Bone Substitutes; D024042:Collagen Type I; D007527:Isoenzymes; C059821:atelocollagen; D003094:Collagen; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase