Effect of proteoglycans at interfaces as related to location, architecture, and mechanical cues

Abstract

Introduction Covalently bound functional GAGs orchestrate tissue mechanics through time-dependent characteristics. Objective The role of specific glycosaminoglycans (GAGs) at the ligament–cementum and cementum–dentin interfaces within a human periodontal complex were examined. Matrix swelling and resistance to compression under health and modeled diseased states was investigated. Materials and methods The presence of keratin sulfate (KS) and chondroitin sulfate (CS) GAGs at the ligament–cementum and cementum–dentin interfaces in human molars (N = 5) was illustrated by using enzymes, atomic force microscopy (AFM), and AFM-based nanoindentation. The change in physical characteristics of modeled diseased states through sequential digestion of keratin sulfate (KS) and chondroitin sulfate (CS) GAGs was investigated. One-way ANOVA tests with P < 0.05 were performed to determine significant differences between groups. Additionally, the presence of mineral within the seemingly hygroscopic interfaces was investigated using transmission electron microscopy. Results Immunohistochemistry (N = 3) indicated presence of biglycan and fibromodulin small leucine rich proteoglycans at the interfaces. Digestion of matrices with enzymes confirmed the presence of KS and CS GAGs at the interfaces by illustrating a change in tissue architecture and mechanics. A significant increase in height (nm), decrease in elastic modulus (GPa), and tissue deformation rate (nm/s) of the PDL-C attachment site (215 ± 63–424 ± 94 nm; 1.5 ± 0.7–0.4 ± 0.2 GPa; 21 ±7–48 ± 22 nm/s), and cementum–dentin interface (122 ± 69–360 ± 159 nm; 2.9 ±1.3–0.7 ±0.3 GPa; 18 ± 4–30 ± 6 nm/s) was observed. Conclusions The sequential removal of GAGs indicated loss in intricate structural hierarchy of hygroscopic interfaces. From a mechanics perspective, GAGs provide tissue recovery/resilience. The results of this study provide insights into the role of GAGs toward conserved tooth movement in the socket in response to mechanical loads, and modulation of potentially deleterious strain at tissue interfaces.

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

“…Bigylcan shows the opposite tendency to aspirin, with localization near the cementum. This is in agreement with previous studies (Kurylo et al, 2016), which have shown biglycan in the cementum. The biglycan positive cells at P21 appear to be in the middle of the PDL space and may migrate to the cementum surface, as seen at P28.…”

“…Proteoglycans have been found to have multiple functions, from cell signaling and regulation of cell differentiation to mechanical properties such as resilience of the ECM to compressive forces (Kurylo et al, 2016). This mechanical property is called thixotropy and has been attributed to proteoglycans in skin (Finlay, 1978).…”

“…They are considered to be the filler component in the ECM and can form large complexes with other proteoglycans and collagens. Proteoglycans contribute to maintaining the structure of the tissue and the ECM and protect the integrity in the face of heavy loading, for example in intervertebral disks (Roughley, 2006), in tendons (Screen et al, 2006), and in the PDL (Kurylo et al, 2016). Beyond their mechanical function, they also modulate growth factors (Zhang et al, 1995;Häkkinen et al, 2000;Kizawa et al, 2005;Yamada et al, 2008;Awata et al, 2015;Yu et al, 2018) and regulate ECM composition and structure (Matheson et al, 2005;Chen and Birk, 2013;Kurylo et al, 2016).…”

Periodontal ligament entheses and their adaptive role in the context of dentoalveolar joint function

“…Several naturally graded interfaces exist in the dynamic joint of the bone-PDL-tooth complex (32, 48–50, 52, 58). A gradual gradient in stiffness between a soft and hard tissue can adapt to an abrupt gradient to accommodate physiologic or non-physiologic demands on joints.…”

“…Regardless, applying principles of mechanics of materials, amplification of strains within the cells at the soft-hard tissue interfaces compared to adjacent bulk tissues per se renders the tethered ends of the softer tissues to be susceptible to increasing shear and flexural moments that are commonly identified in load-bearing joints with short and long-range motions. However, from a mechanics perspective to prevent catastrophic failure of the joint through fatigue, cells interspersed with increased concentrations of matrix molecules including the adhesive proteoglycans (PGs) at these tethered ends (58) can promote cell migration and permit their adhesion and matrix interactions needed for tissue regeneration and remodeling (2). …”