Mechanoadaptive Responses in the Periodontium Are Coordinated by Wnt

Abstract

Despite an extensive literature documenting the adaptive changes of bones and ligaments to mechanical forces, our understanding of how tissues actually mount a coordinated response to physical loading is astonishingly inadequate. Here, using finite element (FE) modeling and an in vivo murine model, we demonstrate the stress distributions within the periodontal ligament (PDL) caused by occlusal hyperloading. In direct response, a spatially restricted pattern of apoptosis is triggered in the stressed PDL, the temporal peak of which is coordinated with a spatially restricted burst in PDL cell proliferation. This culminates in increased collagen deposition and a thicker, stiffer PDL that is adapted to its new hyperloading status. Meanwhile, in the adjacent alveolar bone, hyperloading activates bone resorption, the peak of which is followed by a bone formation phase, leading ultimately to an accelerated rate of mineral apposition and an increase in alveolar bone density. All of these adaptive responses are orchestrated by a population of Wnt-responsive stem/progenitor cells residing in the PDL and bone, whose death and revival are ultimately responsible for directly giving rise to new PDL fibers and new bone.

Mechano‐adaptive Responses of Alveolar Bone to Implant Hyper‐loading in a pre‐clinical in vivo model

“…Actually, we initially hypothesized that implant hyper‐loading would result in microdamage, in view of our previous finding that hyper‐loading of a tooth produced ~ 2% strain in bone (Xu et al., 2019), and the fact that 2% strain is already close to the ultimate strain of 1.8% for cancellous bone with a modulus of 100 MPa (Fyhrie & Vashishth, 2000). So, we were aware that strains of this magnitude may be sufficient to damage bone and observed that the hyper‐loaded tooth had evidence of apoptotic cells in the PDL, which was followed shortly thereafter by extensive bone resorption nearby and ultimately by new bone formation.…”

“…The axial compressive force (i.e., directed toward the sinus) applied to the top surface of an implant in normal and hyper‐loaded state was 1.37 N and 5 N, respectively. These forces were estimated from data on maximal biting forces at the incisal region (Ginot, Herrel, Claude, & Hautier, 2018), a dynamics model that predicted the force at the molar region (Ginot et al., 2018), plus estimates based on laboratory measurements of forces that crushed hard food pellets for rodents (Niver et al., 2011), plus estimates of load‐sharing among molars (Figure 1q and see (Xu et al., 2019)) in the physiological versus hyper‐loaded situations.…”

“…These stresses and strains trigger a combination of catabolic and anabolic responses in bone that ultimately manifest as remodeling (reviewed in (Meakin, Price, & Lanyon, 2014)). Hyper‐loading of the dentition triggers programmed cell death in the PDL and resorption in alveolar bone (Xu et al., 2019). This initial catabolic response is countered by a subsequent anabolic response in which mitotic activity within the PDL is increased and new bone is deposited; together, this anabolic response offsets the catabolic reaction (Xu et al., 2019).…”

“…Hyper‐loading of the dentition triggers programmed cell death in the PDL and resorption in alveolar bone (Xu et al., 2019). This initial catabolic response is countered by a subsequent anabolic response in which mitotic activity within the PDL is increased and new bone is deposited; together, this anabolic response offsets the catabolic reaction (Xu et al., 2019). Here, the aim of this research was to compare the peri‐radicular bone and peri‐implant bone responses to masticatory loading in the normal and hyper‐loading range.…”

A Correlation between Wnt/Beta-catenin Signaling and the Rate of Dentin Secretion

“…Two days after alizarin red injection, the mice were sacrificed and harvested. Samples were fixed in 4% paraformaldehyde overnight, dehydrated with 30% sucrose overnight, and then processed for hard tissue embedding and sectioning using Kawamoto's method 24 . Mineral apposition rates were calculated by measuring the distance between the calcein-labeled bone (green line) and the alizarin red-labeled bone (red line); this measurement was made at 8 distinct, randomly chosen sites around the maxillary first molars in 3 separate mice.…”