Blueprint of an ancestral neurosensory organ revealed in glial networks in human dental pulp

Abstract

Sensory function of human dental pulp has long been known. A composite role has been suggested for odontoblasts as sensory cells in addition to the synthesis of dentinal matrix. However, the neural basis for such a composite sensory activity remains enigmatic. Here, we aimed to probe the question by pursuing an evolutionary logic; if dental pulp is a vestigial sensory organ co-opted to a function of synthesis of mineralized matrix, essential elements of neurosensory organs may persist in dental pulp. Through structural analysis by confocal laser scanning microscopy, three distinct cell populations adjacent to odontoblasts, glial fibrillary acidic protein (GFAP)(+) seracytes, S100(+) telacytes, and HLA-II(+) alacytes were identified in peripheral human dental pulp. Subsequent molecular fingerprinting by quantitative reverse transcriptase-polymerase chain reaction established these cells as analogous to radial glia (GFAP(+) cells), astrocytes (S100(+) cells), and microglia (HLA-II(+) cells) of central nervous system organs. In the cell-rich zone of the pulp, S100(+) cells formed a network, ensheathed unmyelinated axons, and extended end-feet around the capillaries. The microcirculation adjacent to the glial cells in the cell-rich zone possessed ultrastructural features and a gene expression profile typical of the blood-brain barrier system. These novel findings support a new paradigm for understanding sensory functionality of dental pulp by the demonstration of a sophisticated neural structure in the human dental pulp that is analogous to other central sensory organs. Further, the structure that is revealed informs the concept of the evolutionary origin of the dental pulp, suggesting that a neurosensory organ was the precursor structure of teeth.

Glial Network Responses to Polymicrobial Invasion of Dentin

“…The term telacyte (Latin tela = web) was proposed by us for these cells. Telacytes were characterized as astrocyte-like glia by low-level expression of GFAP where the product was not detected immunohistochemically but showed high expression of S100B mRNA in accord with immunologically detected expression of this protein [Farahani et al, 2011]. These cells also expressed genes encoding vascular endothelial growth factor (VEGF) [Virtej et al, 2013], nerve growth factor (NGF) and low-affinity nerve growth factor receptor (P 75 NTR) [Woodnutt et al, 2000].…”

“…Cells intensely reactive with anti-GFAP antibody, and previously termed seracytes by us, were characterized as phenotypically similar to radial glial cells of the central nervous system [Farahani et al, 2011]. Inter-odontoblastic seracytes are distinct in anatomical location and gene expression profile from postnatal stem cells isolated from the central region of dental pulp [Gronthos et al, 2000;Miura et al, 2003], and are also distinct from dental pulp stromal cells derived from dental pulp mesenchymal stem cells [Marchionni et al, 2009;Pivoriuūnas et al, 2010].…”

“…These cells formed intimate attachments to the underlying microvasculature that was characterised as possessing morphological characteristics, including extensive pericytic investment, multiple inter-endothelial tight junctions and endothelial gene expression profile, typical of bloodbrain barrier microvasculature [Farahani et al, 2011].…”

“…In healthy teeth glial cells with the gene expression profile characteristics of radial glial cells of the central nervous system were detected as strongly reactive for glial fibrillary acidic protein (GFAP) and demonstrating a bipolar morphology extending from the odontoblasts to the underlying vasculature [Farahani et al, 2011]. Within the central nervous system radial glia function as precursors of both astrocytic glia and neurons [Sild and Ruthazer, 2011].…”

Tooth Loss Early in Life Accelerates Age-Related Bone Deterioration in Mice

“…Teeth provide a uniquely discriminating sense of touch and directional specificity for occlusal awareness, intra-oral contact for management of a food bolus, discrimination of food texture and hardness, and control of jaw muscles for mastication and swallowing (Klineberg et al 2012). These specific features of teeth are closely linked with the periodontal sensitivity, suggesting an integrated role of the pulp-dentine-enamel complex (Farahani et al 2011). Many studies have shown that poor mastication due to tooth loss, acting as stress, causes various reactions of the autonomic nervous system and endocrine system, activates the hypothalamic-pituitary-adrenal (HPA) axis and transmits to the hypothalamus to increase the release of corticotrophin-releasing hormone (CRH), inducing the secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary, which stimulates the adrenal cortex to produce glucocorticoids, such as cortisol in humans and corticosterone in mice (Levine 2005).…”