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The role of biomineralization in disorders of skeletal development and tooth formation

Abstract

The major mineralized tissues are bone and teeth, which share several mechanisms governing their development and mineralization. This crossover includes the hormones that regulate circulating calcium and phosphate concentrations, and the genes that regulate the differentiation and transdifferentiation of cells. In developing endochondral bone and in developing teeth, parathyroid hormone-related protein (PTHrP) acts in chondrocytes to delay terminal differentiation, thereby increasing the pool of precursor cells. Chondrocytes and (in specific circumstances) pre-odontoblasts can also transdifferentiate into osteoblasts. Moreover, bone and teeth share outcomes when affected by systemic disorders of mineral homeostasis or of the extracellular matrix, and by adverse effects of treatments such as bisphosphonates and fluoride. Unlike bone, teeth have more permanent effects from systemic disorders because they are not remodelled after they are formed. This Review discusses the normal processes of bone and tooth development, followed by disorders that have effects on both bone and teeth, versus disorders that have effects in one without affecting the other. The takeaway message is that bone specialists should know when to screen for dental disorders, just as dental specialists should recognize when a tooth disorder should raise suspicions about a possible underlying bone disorder.

Key points

  • Bone and teeth, the major mineralized tissues, are regulated by many of the same genes and hormones.

  • Parathyroid hormone-related protein acts to delay terminal differentiation in chondrocytes of developing endochondral bone and in developing teeth.

  • Bone and teeth share fates when affected by systemic disorders of mineral homeostasis or of the extracellular matrix.

  • Teeth are not remodelled after they are formed, and so effects of systemic disorders are permanent, whereas bone remodelling can restore the skeleton.

  • Bone specialists and dental specialists should recognize when a disorder of one of the mineralized tissues should raise awareness of a disorder of the other.

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Fig. 1: Normal bone and tooth development.
Fig. 2: Fetal bone and tooth mineralization are dependent on both PTH and PTHrP but not FGF23.
Fig. 3: Developmental pathways of bone and tooth cells.

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Acknowledgements

The authors are supported by Canadian Institutes of Health Research (C.S.K.); Fedération Hospitalo-Universitaire DDS-Paris Net and ANR Hyposkel (C.C.); Fondazione Italiana Ricerca sulle Malattie dell’Osso (M.L.B.); Wellcome Trust Investigator Award (R.V.T.); Wellcome Trust Investigator Award (R.V.T.); National Institute for Health Research (NIHR) Senior Investigator Award (R.V.T.); and NIHR Oxford Biomedical Research Centre Programme (R.V.T.). This article arose out of discussions held at a conference on Biomineralisation in Health and Disease held in Florence, Italy, in 2019 and supported by the Menarini Foundation.

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Glossary

Dentin

A tissue produced by odontoblasts, which are derived from the neural crest. Under the enamel, dentin is similar to bone but is never remodelled under physiological conditions. Dentin surrounds the central (pulp) chamber, which contains odontoblast bodies at its periphery, and mainly consists of connective tissue, blood vessels and nerves.

Cementum

A tissue produced by cementoblasts, which develop from neural crest-derived mesenchymal cells from the connective tissue of the dental follicle. Cementum is a thin layer of hard dental tissue covering the anatomic roots of the teeth.

Enamel

The hardest material of the organism produced biologically by ameloblasts. It is derived from the epithelium and forms the anatomical crown of the teeth.

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Kovacs, C.S., Chaussain, C., Osdoby, P. et al. The role of biomineralization in disorders of skeletal development and tooth formation. Nat Rev Endocrinol 17, 336–349 (2021). https://doi.org/10.1038/s41574-021-00488-z

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