The skeletal system consists of bones and teeth, both of which are hardened via mineralization to support daily physical activity and mastication. The precise mechanism for this process, especially how blood vessels contribute to tissue mineralization, remains incompletely understood. Here, we established an imaging technique to visualize the 3D structure of the tooth vasculature at a single-cell level. Using this technique combined with single-cell RNA sequencing, we identified a unique endothelial subtype specialized to dentinogenesis, a process of tooth mineralization, termed periodontal tip-like endothelial cells. These capillaries exhibit high angiogenic activity and plasticity under the control of odontoblasts; in turn, the capillaries trigger odontoblast maturation. Metabolomic analysis demonstrated that the capillaries perform the phosphate delivery required for dentinogenesis. Taken together, our data identified the fundamental cell-to-cell communications that orchestrate tooth formation, angiogenic–odontogenic coupling, a distinct mechanism compared to the angiogenic–osteogenic coupling in bones. This mechanism contributes to our understanding concerning the functional diversity of organotypic vasculature.
Coupling of angiogenesis and odontogenesis orchestrates tooth mineralization in mice
Disclosures: The authors declare no competing interests exist.
- Award Id(s): 18H05042,18K19553,19H03397
- Award Id(s): JP20gm6210017h0002,21gm6210017h0003
- Award Id(s): JPMJMS 2024
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Tomoko Matsubara, Takahito Iga, Yuki Sugiura, Dai Kusumoto, Tsukasa Sanosaka, Ikue Tai-Nagara, Norihiko Takeda, Guo-Hua Fong, Kosei Ito, Masatsugu Ema, Hideyuki Okano, Jun Kohyama, Makoto Suematsu, Yoshiaki Kubota; Coupling of angiogenesis and odontogenesis orchestrates tooth mineralization in mice. J Exp Med 4 April 2022; 219 (4): e20211789. doi: https://doi.org/10.1084/jem.20211789
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