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Autophagy Regulates Craniofacial Bone Acquisition

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Abstract

Increasing evidence has demonstrated the important role of autophagy in skeletal homeostasis; however, the role of autophagy in craniofacial bone development and acquisition is largely unknown. In this study, we investigated the effect of autophagy suppression on craniofacial bone acquisition by deleting Fip200 or Atg5, two essential autophagy genes, using Osterix-Cre (Osx-Cre). We found that the Osx-Cre transgene mildly decreased the bone mass of parietal bone but not frontal bone, and did not affect cranial base bone mass in adult mice. In the cranial vault, Fip200 or Atg5 deletion similarly decreased 50% bone mass of neural crest-derived frontal bone; Atg5 deletion decreased 50% and Fip200 deletion decreased 30% bone mass of mesoderm-derived parietal bone. In the cranial base, Fip200 or Atg5 deletion similarly decreased 30% bone mass of neural crest-derived presphenoid bone; Atg5 deletion decreased 30% and Fip200 deletion decreased 16% bone mass of mesoderm-derive basioccipital bone. Lastly, we used doxycycline treatment to inhibit the Osx-Cre expression until 2 months of age and showed that postnatal Fip200 deletion led to cranial vault bone mass decrease in association with a small increase in both bone volume/tissue volume and tissue mineral density. Altogether, this study demonstrated the important role of autophagy in craniofacial bone acquisition during development and postnatal growth.

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Acknowledgements

We thank Dr. Noboru Mizushima for providing the Atg5 floxed mice. This study was funded by the NIH (Grant Nos. AR062030 to F.L, NS094144 to JG) and University of Michigan School of Dentistry Research Pathway fund (to N.T). MicroCT work was partly supported by P30 Core Center award to University of Michigan from NIAMS (AR 69620).

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  1. Neil Thomas, Han Kyoung Choi, and Xiaoxi Wei contributed equally to this work.

Authors and Affiliations

  1. Department of Biologic and Materials Sciences & Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI, 48109, USA

    Neil Thomas, Han Kyoung Choi, Xiaoxi Wei, Li Wang, Yuji Mishina & Fei Liu

  2. Department of Orthodontics, Jilin University School and Hospital of Stomatology, Changchun, 130021, Jilin, China

    Xiaoxi Wei

  3. Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 45267, USA

    Jun-Lin Guan

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  1. Neil Thomas
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Correspondence to Fei Liu.

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Neil Thomas, Han Kyoung Choi, Xiaoxi Wei, Li Wang, Yuji Mishina, Jun-Lin Guan, and Fei Liu declare that they have no conflict of interest.

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This article does not contain any studies with human subjects performed by any of the authors. All mice procedures used in this study were approved by the Institutional Animal Care and Use Committee at the University of Michigan.

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Thomas, N., Choi, H.K., Wei, X. et al. Autophagy Regulates Craniofacial Bone Acquisition. Calcif Tissue Int 105, 518–530 (2019). https://doi.org/10.1007/s00223-019-00593-2

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