Local injection of RANKL facilitates tooth movement and alveolar bone remodelling

Abstract

Objectives To investigate the effect of local injection of receptor activator of nuclear factor kappa B ligand (RANKL) on experimental tooth movement and subsequent alveolar bone remodelling in mice. Materials and Methods Sixty mice were randomised to receive daily local RANKL or phosphate‐buffered saline injections in the buccal premaxillary bone for 14 of 21 days of incisor movement, followed by a 21‐day retention period. Five mice from each group were euthanised on days 0, 3, 7, 14, 21 and 42, and specimens were prepared for haematoxylin and eosin, tartrate‐resistant acid phosphatase and immunohistochemical staining. Five mice from each group were subjected to serial microcomputed tomography until day 42 for tooth movement and bone volume quantification. Results The experimental group showed significantly greater tooth movement and bone volume reduction on days 14 and 21; an increased osteoclast number on days 3, 7, 14 and 21; and no difference on day 42. Higher RANKL expression was observed on days 7 and 14, with remarkable alkaline phosphatase activity. No significant systemic changes were observed. Conclusion Local RANKL injection leads to increased osteoclastic activity and facilitates tooth movement, followed by subsequent alveolar bone formation; this implies a reversible transitional acceleration of bone resorption.

Modulating OPG and TGF-β1 mRNA expression via bioelectrical stimulation

“…On the other hand, the induction of tooth fixation, by way of increased OPG expression, stops bone softening by reducing osteoclastogenesis and promoting bone hardening ( Baud’huin et al, 2013 ). Previous studies involving the injection of OPG directly into dental tissues have also proven successful ( Baxter et al, 2020 ; Li et al, 2019 ; Li and Tang, 2009 ), although application can become stressful and painful to the patient during multiple treatments. This study documents that an alternative method, bioelectric stimulation, can increase the concentration of OPG and TGF-β1 mRNA expression within osteoblasts, leading to a potentially non-invasive alternative to increasing OPG expression without the associated risk and discomfort of repeat OPG injections.…”

Targeting the RANKL/RANK/OPG Axis for Cancer Therapy

“…Factors that can induce bone resorption, such as the sex hormone progesterone, vitamin D3, PTHrP, IL-1, IL-11, IL-17, or TNF-α ( 19 – 23 ) act on osteoblasts to induce RANKL expression, which then binds to its receptor RANK on the surface of osteoclast progenitor cells, inducing pre-osteoclast differentiation into multinucleated, fully-functional osteoclasts. RANKL also plays an important role in the continued survival and function of osteoclasts ( 24 – 27 ) ( Figure 1 ). RANKL is produced as a membrane-bound protein which can also be shed as a soluble trimeric protein ( 28 ).…”

H‐type blood vessels participate in alveolar bone remodeling during murine tooth extraction healing

“…Bone remodeling process consists of osteoclast‐mediated bone resorption and osteoblast‐mediated bone formation (Ishii, Kikuta, Shimazu, Meier‐Schellersheim, & Germain, 2010; Johnson, Schipani, & Giaccia, 2015). Currently, bisphosphonates (Davis et al, 2016; Shannon, Shannon, Modelevsky, & Grippo, 2011), parathyroid hormone (PTH) (Chandra et al, 2014; Smit, Kinschot, Linden, Noord, & Kos, 2019), and nuclear factor kappa B ligand (RANKL) inhibition (Ikebuchi et al, 2018; Li, Chung, Hwang, & Lee, 2019) are used to modulate bone remodeling and prevent bone loss. Nevertheless, approaches to effectively increase bone formation without affecting normal bone remodeling remain to be developed.…”