Molecular Variations Related to the Regional Differences in Periosteal Growth at the Mandibular Ramus

Abstract

Periosteal growth at human mandibular ramus is characterized by bone apposition at the posterior border and resorption at the anterior border. Molecular control of this regional variation is unclear. This study examined the expression of several molecules involved in bone apposition/ resorption at these regions in vivo and in vitro. By using growing pigs as a model, the periosteal growth was assessed at the mandibular ramus by vital staining and histological observations. In parallel, periosteal tissues were harvested and pulverized for RNA and protein extraction. Periosteal cells were also isolated, expanded in osteogenic media, and subjected to a single dose of dynamic tensile strain (0, 5, or 10% magnitude at 0.5 Hz) to examine their responses to mechanical loading. Real-time RT-PCR and Western blot analyses were used to examine mRNA and protein expression from periosteal tissues and cultured cells. Histological observation confirmed an anterior-resorption/posterior-apposition pattern in the pig mandibular ramus. Both in vivo tissue and in vitro cells demonstrated greater mRNA expression of receptor activator of NF-jB ligand (RANKL)/osteoprotegerin (OPG) ratio and bone morphogenetic protein 2 (BMP2) at the anterior region, while OPG expression at the anterior region was lower than the posterior region. In response to the application of a single dose of dynamic tensile strain, cultured periosteal cells appeared to change the expression profile of osteogenic markers but not that of RANKL/OPG and BMP2. These findings suggest that the unique regional variation of periosteal activity at the mandibular ramus is regulated by a differential expression of RANKL/OPG ratio (likely through differential induction of OPG) and BMP2. Anat Rec, 294:79-87, 2011. V V C 2010 Wiley-Liss, Inc.Key words: periosteum; mandibular growth; RANKL/OPG; tissue engineering; cell loadingHuman mandibular growth is mainly through endochondral bone formation at the condyles and intramembranous bone formation at the periosteum (Enlow and Hans, 1996). While condylar growth provides the overall elongation and rotation of the mandible (Bjork and Skieller, 1983), periosteal activity causes extensive surface modeling/remodeling or reshaping of the mandible (Enlow and Hans, 1996). One striking feature of mandibular periosteal activity is at the ramus, where bone resorption takes place at the anterior (rostral) border whereas bone apposition at the posterior (caudal) border (Robinson and Sarnat, 1955;Seiton and Engel, 1969;Hans et al., 1995). At the cell level, osteogenic proliferation is concentrated at the appositional posterior ramal region, whereas osteoclasts are mainly present at the resorptive anterior region (Ochareon and Herring, 2007). However, the molecular mechanisms related to these differential periosteal activities are mostly unknown.

The complex ontogenetic trajectory of mandibular shape in a laboratory mouse

“…Some studies suggest that these changes, as well as outgrowth and the posterior cartilages, can be influenced by hormonal disruptions (Fujita et al 2004;Ramirez-Yañez et al 2005), muscle development mutations (Lightfoot & German, 1998;Nicholson et al 2006;Ravosa et al 2007;Rot-Nikcevic et al 2007;Renaud et al 2010;Vecchione et al 2010), changes in food hardness or consistency (He & Kiliaridis, 2003;Mavropoulos et al 2005), and orthodontic manipulation (Mavropoulos et al 2005;Shen et al 2006). Yet, it remains unclear what regulates the spatial distribution of those signals during normal growth to produce the ontogenetic sequence of shapes (Nicholson et al 2006;Hsiao et al 2010;Sun & Tee, 2011). The results of this study suggest that this spatial distribution is repatterned twice during postnatal growth of the Mus mandible to produce the sharp changes in the direction of its ontogenetic trajectory.…”

“…; Hsiao et al. ; Sun & Tee, ). The results of this study suggest that this spatial distribution is repatterned twice during postnatal growth of the Mus mandible to produce the sharp changes in the direction of its ontogenetic trajectory.…”

Scaffold-Based Delivery of Autologous Mesenchymal Stem Cells for Mandibular Distraction Osteogenesis: Preliminary Studies in a Porcine Model

“…The expression levels of runt-related transcription factor-2 (Runx2), osteocalcin (OCN) and bone morphogenetic protein 2 (BMP-2) were assessed using RT-qPCR assay as previously described [32]. Total RNA was isolated from the BM-MSCs using RNeasy Mini Kit (Qiagen, Valencia, CA) and was quantified by Nanodrop 1000 (Thermo Scientific, Waltham, MA).…”

Culture‐expanded mesenchymal stem cell sheets enhance extraction‐site alveolar bone growth: An animal study

“…At postoperative week 6 and 3 days after the alizarin labeling, the pigs were killed with an intravenous injection of potassium chloride while being deeply anesthetized. Alveolar specimens containing the extraction sites were immediately harvested for subsequent radiographic and histological analyses …”

“…While these changes are due to bone resorption in the adult patient, they mainly result from decelerated growth at the buccal bone surface after tooth extraction . Similar to other mandibular surfaces, intramembranous bone formation that originated from the periosteum determines the contour, thickness and density of the buccal cortical plate. Thus, a plausible approach to prevent growth deceleration at the buccal alveolar surface is to augment the osteogenic potential of the periosteum.…”