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Chronological histological changes during bone regeneration on a non-crosslinked atelocollagen matrix

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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.

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Acknowledgments

We thank Dr. I Fujimoto (Koken Co., Ltd. Research Institute) for critical discussion and technical assistance for type I collagen. This work was supported by Grant-in-Aid for Scientific Research from MEXT/JSPS (KAKENHI Grant Number 21390491 and 24390409 to S.T. and 24792075 to R.K.).

Conflict of interest

All authors have no conflicts of interest.

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Authors and Affiliations

  1. Department of Oral Pathology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Ryosuke Kagawa, Mitsunobu Kishino, Sunao Sato, Ken Ishida, Yuzo Ogawa & Satoru Toyosawa

  2. Department of Prosthodontics, Gerodontology and Oral Rehabilitation, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Ryosuke Kagawa, Ken Ishida, Kazunori Ikebe & Yoshinobu Maeda

  3. Division for Interdisciplinary Dentistry, Osaka University Faculty of Dentistry, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Kaori Oya

  4. Division of Materials and Manufacturing Science, Osaka University Graduate School of Engineering, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Takuya Ishimoto & Takayoshi Nakano

  5. Department of Developmental and Reconstructive Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8523, Japan

    Toshihisa Komori

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  1. Ryosuke Kagawa
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  11. Toshihisa Komori
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Correspondence to Satoru Toyosawa.

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Kagawa, R., Kishino, M., Sato, S. et al. Chronological histological changes during bone regeneration on a non-crosslinked atelocollagen matrix. J Bone Miner Metab 30, 638–650 (2012). https://doi.org/10.1007/s00774-012-0376-y

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  • DOI: https://doi.org/10.1007/s00774-012-0376-y

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