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Formation of bone-like tissue by dental follicle cells co-cultured with dental papilla cells

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Abstract

During tooth root formation, dental follicle cells (DFCs) differentiate into osteoblasts/cementoblasts when they are in contact with pre-existing dentin. Since some factors of dentin matrix were also produced by dental papilla cells (DPCs) and could induce DFCs differentiation, we hypothesized that DPCs can directly promote DFCs differentiation and that differentiation could occur in a co-culture model. To test this hypothesis, we investigated the characteristics of DFCs that are influenced by DPCs in an in vitro co-culture and in vivo heterotopic transplant model. One week into the co-culture, there were significant increases in the mRNA level of bone morphogenetic protein 2 (BMP2), osteoprotegerin (OPG), bone sialoprotein (BSP) and osteocalcin (OCN), and a decrease of the receptor activator of nuclear factor κB ligand (RANKL). Additionally, the number of BMP2-, OPG-, BSP- and OCN-positive DFCs increased whereas RANKL-positive DFCs decreased. Three weeks after co-culture, DFCs produced calcified nodules, accompanied with increased sub-cellular organelles for protein synthesis and secretion. In the heterotopic transplant model, the adult male rats were used as hosts, DFCs were transplanted into the omentum. In vivo 5-week growth of DFCs in the presence of DPCs led to the formation of bone-like tissues, positive for BSP, OCN and BMP2. In contrast, DFCs alone led to fibrous-like tissues. These results indicated that in the absence of pre-existing dentin, DPCs can stimulate osteogenesis and inhibit osteoclastogenesis in DFCs and suggested a novel strategy to promote DFCs differentiation.

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Acknowledgments

We are grateful to Dr. Takashi Muramatsu and Yasunobu Enokiya (Department of Pathology, Tokyo Dental College) for kindly providing BMP2 primer and antibody. We are also grateful to Dr. Fumiko Fukuhara, Dr. Sachie Sennzui (Department of Pediatric Dentistry, Tokyo Dental College), Mr. Tatokoro and Ms. Takano for advice and technology help in the experiments.

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Authors and Affiliations

  1. Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, 145 West Changle Road, Xi’an, 710032, China

    Yudi Bai & Xiaojing Wang

  2. Department of Clinical Pathophysiology and Oral Health Science Center, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba, 261-0012, Japan

    Yudi Bai, Kenichi Matsuzaka, Eitoyo Kokubu & Takashi Inoue

  3. Department of Health Statistics, Fourth Military Medical University, Xi’an, 710032, China

    Yuxiang Bai

  4. Department of Pathology, Tokyo Dental College, Chiba, 261-0012, Japan

    Sadamitsu Hashimoto

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  1. Yudi Bai
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  2. Yuxiang Bai
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  3. Kenichi Matsuzaka
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  4. Sadamitsu Hashimoto
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  5. Eitoyo Kokubu
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  6. Xiaojing Wang
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  7. Takashi Inoue
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Corresponding authors

Correspondence to Xiaojing Wang or Takashi Inoue.

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Yudi Bai and Yuxiang Bai contributed equally to this work.

This work was supported partly by the Sasagawa Fellowship.

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Bai, Y., Bai, Y., Matsuzaka, K. et al. Formation of bone-like tissue by dental follicle cells co-cultured with dental papilla cells. Cell Tissue Res 342, 221–231 (2010). https://doi.org/10.1007/s00441-010-1046-9

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