Notch Coordinates Periodontal Ligament Maturation through Regulating Lamin A

Abstract

Tooth eruption is a continuous biological process with dynamic changes at cellular and tissue levels, particularly within the periodontal ligament (PDL). Occlusion completion is a significant physiological landmark of dentition establishment. However, the importance of the involvement of molecular networks engaging in occlusion establishment on the final PDL maturation is still largely unknown. In this study, using rat and mouse molar teeth and a human PDL cell line for RNAseq and proteomic analysis, we systematically screened the key molecular links in regulating PDL maturation before and after occlusion establishment. We discovered Notch, a key molecular pathway in regulating stem cell fate and differentiation, is a major player in the event. Intercepting the Notch pathway by deleting its key canonical transcriptional factor, RBP-Jkappa, using a conditional knockout strategy in the mice delayed PDL maturation. We also identified that Lamin A, a cell nuclear lamina member, is a unique marker of PDL maturation, and its expression is under the control of Notch signaling. Our study therefore provides a deep insight of how PDL maturation is regulated at the molecular level, and we expect the outcomes to be applied for a better understanding of the molecular regulation networks in physiological conditions such as tooth eruption and movement and also for periodontal diseases.

Oleic acid-related anti-inflammatory effects in force-stressed PdL fibroblasts are mediated by H3 lysine acetylation associated with altered IL10 expression

“…In this study, perpendicular compressive forces on parallel-aligned cells triggered decreased HDAC activity leading to increased histone acetylation. This pathway, presumably mediated by the nuclear matrix protein lamin A/C [55], may be of interest because PdL cells also exhibit robust lamin A/C expression that is even increased in a force-dependent manner for lamin A [56]. In this aspect, in several cell types oleic acid treatment triggered the formation of lamin A/C-positive nuclear tubules [57], which are important for calcium homeostasis that can considerably affect histone acetylation [58].…”

Core Matrisome Protein Signature During Periodontal Ligament Maturation From Pre-occlusal Eruption to Occlusal Function

“…This is a mechano-sensitive process (Jacobs et al, 2013). PDL fibroblasts have been shown to respond to mechanical strain by activation of molecules like Piezo-1 (Jin et al, 2014), β-2 adrenergic receptor (Adrb2) (Cao et al, 2014), prostaglandin (PG) E2/cyclooxygenase (COX)-2 (Römer et al, 2013) and Notch (Kikuta et al, 2015;Denes et al, 2019). Thus similarly to forces occurring during orthodontic tooth movement, masticatory forces seem to produce an osteogenic response in the PDL, possibly to remodel the alveolar socket shape or to reorganize Sharpey's fibers.…”

From the Matrix to the Nucleus and Back: Mechanobiology in the Light of Health, Pathologies, and Regeneration of Oral Periodontal Tissues

“…The Notch pathway is involved in this process and responds to cell-to-cell and cellto-matrix mechanical cues. Of interest, a transcriptional downstream target of mechanically activated Notch signaling in the PDL is Lamin A, whose Notch signaling-derived increase in expression supports the notion of the involvement of NMT in the periodontium [221].…”