Axonal Degeneration in Dental Pulp Precedes Human Primary Teeth Exfoliation

Abstract

The dental pulp in human primary teeth is densely innervated by a plethora of nerve endings at the coronal pulp-dentin interface. This study analyzed how the physiological root resorption (PRR) process affects dental pulp innervation before exfoliation of primary teeth. Forty-four primary canine teeth, classified into 3 defined PRR stages (early, middle, and advanced) were fixed and demineralized. Longitudinal cryosections of each tooth were stained for immunohistochemical and quantitative analysis of dental pulp nerve fibers and associated components with confocal and electron microscopy. During PRR, axonal degeneration was prominent and progressive in a Wallerian-like scheme, comprising nerve fiber bundles and nerve endings within the coronal and root pulp. Neurofilament fragmentation increased significantly during PRR progression and was accompanied by myelin degradation and a progressive loss of myelinated axons. Myelin sheath degradation involved activation of autophagic activity by Schwann cells to remove myelin debris. These cells expressed a sequence of responses comprising dedifferentiation, proliferative activity, GAP-43 overexpression, and Büngner band formation. During the advanced PRR stage, increased immune cell recruitment within the dental pulp and major histocompatibility complex (MHC) class II upregulation by Schwann cells characterized an inflammatory condition associated with the denervation process in preexfoliative primary teeth. The ensuing loss of dental pulp axons is likely to be responsible for the progressive reduction of sensory function of the dental pulp during preexfoliative stages.

The repair Schwann cell and its function in regenerating nerves

“…3). Autophagy of myelin has also been seen in Schwann cells during axonal degeneration in the dental pulp (Suzuki et al 2015).…”

“…Third, an important function of denervated cells, but not immature cells, is to organize the clearance of myelin, indirectly by macrophage recruitment and directly by myelin autophagy (myelinophagy) (reviewed in Hirata & Kawabuchi, 2002;Gomez-Sanchez et al 2015;Suzuki et al 2015).…”

Repair Schwann cell update: Adaptive reprogramming, EMT, and stemness in regenerating nerves

“…These cells often carry long, parallel processes, which together with their length, allows repair cells to partly overlap and promotes the formation of the compact cellular columns (Bungner bands—Figures and ), which are obligatory regeneration tracks for regenerating axons (Gomez‐Sanchez et al, ). (d) Activation of myelinophagy by which myelin cells initiate the breakdown of their own myelin sheath (Gomez‐Sanchez et al, , Suzuki, Lovera, Schmachtenberg, & Couve, ; Jang et al, ; Brosius Lutz et al, ).…”

After Nerve Injury, Lineage Tracing Shows That Myelin and Remak Schwann Cells Elongate Extensively and Branch to Form Repair Schwann Cells, Which Shorten Radically on Remyelination

“…Signaling mechanisms activated after injury, such as the P38, JNK, and Erk1/2 MAP kinase pathways and gpr126 and histone deacetylase 2 (HDAC2), have also been studied (for review, see Boerboom et al, 2017 ). Schwann-cell-derived trophic factors, which potentially support regeneration have been examined (for review, see Boyd and Gordon, 2003 ; Chen et al, 2007; Scheib and Höke, 2013 ; Wood and Mackinnon, 2015) and mechanisms of myelin clearance including myelinophagy and macrophage recruitment have been identified ( Hirata and Kawabuchi, 2002 ; Gomez-Sanchez et al, 2015 ; Suzuki et al, 2015 ).…”