GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by P. gingivalis LPS and Concurrent Compression

Periodontitis is characterized by bacterially induced inflammatory destruction of periodontal tissue. This also affects fibroblasts of the human periodontal ligaments (HPdLF), which play a coordinating role in force-induced tissue and alveolar bone remodeling. Excessive inflammation in the oral tissues has been observed with simultaneous stimulation by pathogens and mechanical forces. Recently, elevated levels of growth differentiation factor 15 (GDF15), an immuno-modulatory member of the transforming growth factor (TGFB) superfamily, were detected under periodontitis-like conditions and in force-stressed PdL cells. In view of the pleiotropic effects of GDF15 in various tissues, this study aims to investigate the role of GDF15 in P. gingivalis-related inflammation of HPdLF and its effect on the excessive inflammatory response to concurrent compressive stress. To this end, the expression and secretion of cytokines (IL6, IL8, COX2/PGE2, TNFα) and the activation of THP1 monocytic cells were analyzed in GDF15 siRNA-treated HPdLF stimulated with P. gingivalis lipopolysaccharides alone and in combination with compressive force. GDF15 knockdown significantly reduced cytokine levels and THP1 activation in LPS-stimulated HPdLF, which was less pronounced with additional compressive stress. Overall, our data suggest a pro-inflammatory role for GDF15 in periodontal disease and demonstrate that GDF15 partially modulates the force-induced excessive inflammatory response of PdLF under these conditions.

Difference in the Alveolar Bone Remodeling Between the Adolescents and Adults During Upper Incisor Retraction: a Retrospective Study

Background: The purpose of this study was to compare the difference of alveolar bone remodeling between the adolescents and adults in the maxillary incisor area during retraction. Methods: This retrospective study included 72 female patients who needed moderate anchorage to correct the bimaxillary protrusion. Subjects were further divided into the minor group (n=36, 11-16 years old) and adult group (n=36, 18-35 years old). Digital lateral cephalography and cone beam CT scanning were taken in each patient before (T0) and after treatment (T1). Cephalometry was conducted to assess incisor retraction, while alveolar bone thickness (ABT), alveolar bone distance (ABD, and alveolar bone area (ABA) were detected to assess changes in the alveolar bone. Results: No difference in the inclination of upper incisors was observed at both T0 and T1. Changes in the alveolar bone showed a similar tendency with bone apposition on the labial side and resorption on the palatal side. Less increase in the labial ABT (T1-T0) and more decrease in the palatal ABT (T1-T0) was found in the adult group, leading to less total ABT in the adult group. Higher reduction inn ABD (T1-T0) was found in the adult group. Moreover, more decrease in the ABA (T1-T0) was found in the adult group. Conclusion: When compared adolescents, adult patients have less alveolar bone support after orthodontic treatment, showing a through-the-bone remodeling pattern. Orthodontic should take the age into consideration to reduce the potential periodontal risks during treatment planning.

Mechanosensitive Piezo1 in Periodontal Ligament Cells Promotes Alveolar Bone Remodeling During Orthodontic Tooth Movement

Orthodontic tooth movement (OTM) is a process depending on the remodeling of periodontal tissues surrounding the roots. Orthodontic forces trigger the conversion of mechanical stimuli into intercellular chemical signals within periodontal ligament (PDL) cells, activating alveolar bone remodeling, and thereby, initiating OTM. Recently, the mechanosensitive ion channel Piezo1 has been found to play pivotal roles in the different types of human cells by transforming external physical stimuli into intercellular chemical signals. However, the function of Piezo1 during the mechanotransduction process of PDL cells has rarely been reported. Herein, we established a rat OTM model to study the potential role of Piezo1 during the mechanotransduction process of PDL cells and investigate its effects on the tension side of alveolar bone remodeling. A total of 60 male Sprague-Dawley rats were randomly assigned into three groups: the OTM + inhibitor (INH) group, the OTM group, and the control (CON) group. Nickel-titanium orthodontic springs were applied to trigger tooth movement. Mice were sacrificed on days 0, 3, 7, and 14 after orthodontic movement for the radiographic, histological, immunohistochemical, and molecular biological analyses. Our results revealed that the Piezo1 channel was activated by orthodontic force and mainly expressed in the PDL cells during the whole tooth movement period. The activation of the Piezo1 channel was essential for maintaining the rate of orthodontic tooth movement and facilitation of new alveolar bone formation on the tension side. Reduced osteogenesis-associated transcription factors such as Runt-related transcription factor 2 (RUNX2), Osterix (OSX), and receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) ratio were examined when the function of Piezo1 was inhibited. In summary, Piezo1 plays a critical role in mediating both the osteogenesis and osteoclastic activities on the tension side during OTM.

Craniofacial Characteristics and Orthodontic Treatment of Diamond Blackfan Syndrome: Two Case Reports

Diamond Blackfan anemia (DBA) is a chronic congenital form of erythrocytic hypoplasia in which erythroid precursor cell levels are low. DBA reflects ribosomal dysfunction and is accompanied by hematopoietic cell apoptosis, anemia, and various somatic symptoms. We report the characteristic symptoms of the craniofacial region and the orthodontic treatments of two DBA cases. Case 1 was a 12-year-old female. The typical physical and facial characteristics of DBA were lacking. On initial examination, she exhibited a skeletal Class II jaw and end to end molar relationships and a large overjet. An edgewise appliance was placed after extraction of the first maxillary premolars. After 3 years and 11 months, an appropriate overjet and overbite, rigid intercuspation, and an acceptable profile were evident without any clinical adverse effects. Case 2 was a 13-year-old female. She exhibited a skeletal Class I jaw relationship, a spaced dental arch, the maxillofacial dysplasia characteristic of Binder syndrome, hypoplasia of the right mandibular condyle, and labial protrusions of the maxillary and mandibular incisors. We placed an edgewise appliance and after 1 year and 7 months, the occlusion was optimal in the absence of any adverse effects. Our two DBA cases exhibited a broad spectrum of physical and dentofacial symptoms. Patients with DBA are often prescribed combined steroid/bisphosphonate therapies. Both agents are likely to affect alveolar bone remodeling after tooth extraction and orthodontic tooth movement. Careful consideration of medication with reference to various dentofacial characteristics is necessary.

Oral Osteomicrobiology: The Role of Oral Microbiota in Alveolar Bone Homeostasis

Osteomicrobiology is a new research field in which the aim is to explore the role of microbiota in bone homeostasis. The alveolar bone is that part of the maxilla and mandible that supports the teeth. It is now evident that naturally occurring alveolar bone loss is considerably stunted in germ-free mice compared with specific-pathogen-free mice. Recently, the roles of oral microbiota in modulating host defense systems and alveolar bone homeostasis have attracted increasing attention. Moreover, the mechanistic understanding of oral microbiota in mediating alveolar bone remodeling processes is undergoing rapid progress due to the advancement in technology. In this review, to provide insight into the role of oral microbiota in alveolar bone homeostasis, we introduced the term “oral osteomicrobiology.” We discussed regulation of alveolar bone development and bone loss by oral microbiota under physiological and pathological conditions. We also focused on the signaling pathways involved in oral osteomicrobiology and discussed the bridging role of osteoimmunity and influencing factors in this process. Finally, the critical techniques for osteomicrobiological investigations were introduced.

Effect of Curcumin on Alterations of Alveolar Bone Remodeling and Expression of Receptor Activator of Nuclear Factor-κ B Ligand in Rat Tooth During Tooth Movement

Objective: To evaluate the effect of Curcumin on Alterations of Alveolar Bone Remodeling and Expression of RANKL in Rat Tooth during Tooth Movement. Methods: 64 SD rats were randomly divided into 4 groups, Model, Adrb2, Cur and Cur + Pro groups. The rat orthodontic teeth movement models were established.The rats were injected corresponding reagents according to weight and were sacrificed on day 0, 7, 14 and 21. The movement distance of first molar of rats was measured by Vernier caliper.The numbers of osteoclasts were observed through TRAP staining. The change of micro-structure of alveolar bone was evaluated by Micro-CT. Results: The trends of the distance of teeth movement and numbers of osteoclast were the same: Cur group β Adrb2 group > Model groups Cur+Pro group (P < 0.05). Micro-CT scan showed that curcumin could reduce the bone volume fraction (BV/TV), bone trabecular density (MTPD), and increase the trabecular resolution (TB. SP). When propranolol was given at the same time, the effect of curcumin disappeared. Conclusion: Curcumin could promote the resorption of alveolar bone at the pressure side and increase the osteoclast numbers so that the alveolar bone became looser which was beneficial to the movement of orthodontic tooth.

Orthodontic Force–Induced BMAL1 in PDLCs Is a Vital Osteoclastic Activator

Orthodontic tooth movement (OTM) depends on periodontal ligament cells (PDLCs) sensing biomechanical stimuli and subsequently releasing signals to initiate alveolar bone remodeling. However, the mechanisms by which PDLCs sense biomechanical stimuli and affect osteoclastic activities are still unclear. This study demonstrates that the core circadian protein aryl hydrocarbon receptor nuclear translocator–like protein 1 (BMAL1) in PDLCs is highly involved in sensing and delivering biomechanical signals. Orthodontic force upregulates BMAL1 expression in periodontal tissues and cultured PDLCs in manners dependent on ERK (extracellular signal–regulated kinase) and AP1 (activator protein 1). Increased BMAL1 expression can enhance secretion of CCL2 (C-C motif chemokine 2) and RANKL (receptor activator of nuclear factor–κB ligand) in PDLCs, which subsequently promotes the recruitment of monocytes that differentiate into osteoclasts. The mechanistic delineation clarifies that AP1 induced by orthodontic force can directly interact with the BMAL1 promoter and activate gene transcription in PDLCs. Localized administration of the ERK phosphorylation inhibitor U0126 or the BMAL1 inhibitor GSK4112 suppressed ERK/AP1/BMAL1 signaling. These treatments dramatically reduced osteoclastic activity in the compression side of a rat orthodontic model, and the OTM rate was almost nonexistent. In summary, our results suggest that force-induced expression of BMAL1 in PDLCs is closely involved in controlling osteoclastic activities during OTM and plays a vital role in alveolar bone remodeling. It could be a useful therapeutic target for accelerating the OTM rate and controlling pathologic bone-remodeling activities.