Alliances of the gut and bone axis.

Gut hormones secreted from enteroendocrine cells following nutrient ingestion modulate metabolic processes including glucose homeostasis and food intake, and several of these gut hormones are involved in the regulation of the energy demanding process of bone remodelling. Here, we review the gut hormones considered or known to be involved in the gut-bone crosstalk and their role in orchestrating adaptions of bone formation and resorption as demonstrated in cellular and physiological experiments and clinical trials. Understanding the physiology and pathophysiology of the gut-bone axis may identify adverse effects of investigational drugs aimed to treat metabolic diseases such as type 2 diabetes and obesity and new therapeutic candidates for the treatment of bone diseases.

Peripheral nerve-derived Sema3A promotes osteogenic differentiation of mesenchymal stem cells through the Wnt/ß-catenin/Nrp1 positive feedback loop.

Sensory nerves play a crucial role in maintaining bone homeostasis by releasing Semaphorin 3A (Sema3A). However, the specific mechanism of Sema3A in regulation of bone marrow mesenchymal stem cells (BMMSCs) during bone remodelling remains unclear. The tibial denervation model was used and the denervated tibia exhibited significantly lower mass as compared to sham operated bones. In vitro, BMMSCs cocultured with dorsal root ganglion cells (DRGs) or stimulated by Sema3A could promote osteogenic differentiation through the Wnt/ß-catenin/Nrp1 positive feedback loop, and the enhancement of osteogenic activity could be inhibited by SM345431 (Sema3A-specific inhibitor). In addition, Sema3A-stimulated BMMSCs or intravenous injection of Sema3A could promote new bone formation in vivo. To sum up, the coregulation of bone remodelling is due to the ageing of BMMSCs and increased osteoclast activity. Furthermore, the sensory neurotransmitter Sema3A promotes osteogenic differentiation of BMMSCs via Wnt/ß-catenin/Nrp1 positive feedback loop, thus promoting osteogenesis in vivo and in vitro.

Is RANKL a potential molecular target in osteoarthritis?

OBJECTIVE: Osteoarthritis (OA) is a disease of joints, in which the bone under the articular cartilage undergoes increased remodelling activity. The question is whether a better understanding of the causes and mechanisms of bone remodelling can predict disease-modifying treatments. DESIGN: This review summarises the current understanding of the aetiology of OA, with an emphasis on events in the subchondral bone (SCB), and the cells and cytokines involved, to seek an answer to this question. RESULTS: SCB remodelling across OA changes the microstructure of the SCB, which alters the load-bearing properties of the joint and seems to have an important role in the initiation and progression of OA. Bone remodelling is tightly controlled by numerous cytokines, of which Receptor Activator of NFκB ligand (RANKL) and osteoprotegerin are central factors in almost all known bone conditions. In terms of finding therapeutic options for OA, an important question is whether controlling the rate of SCB remodelling would be beneficial. The role of RANKL in the pathogenesis and progression of OA and the effect of its neutralisation remain to be clarified. CONCLUSIONS: This review further makes the case for SCB remodelling as important in OA and for additional study of RANKL in OA, both its pathophysiological role and its potential as an OA disease target.

Treatment Effect of Zoledronic Acid in Chronic Non-bacterial Osteomyelitis of the Jaw: A Case Series.

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory, osteolytic bone disorder sometimes localized to a unifocal site in the jaw, causing long-term pain and reduced function. The aim of this study was to describe the patients with CNO of the jaw, focusing on treatment with zoledronic acid for pain relief. An analysis of medical records of 24 patients with CNO of the jaw, including treatment with zoledronic acid and effects on pain relief. Descriptive statistics and nonparametric tests were used to describe the population and compare treatment effects, respectively. The average treatment period was 33.4 months (median 23; Q1 11.5; Q3 42.0) with an average of 4.1 infusions (median 3; Q1 2; Q3 5) of zoledronic acid. The average pain VAS score (visual analogue scale) was significantly reduced from 7.7 (median 8; Q1 6.5; Q3 8.5) to 2.5 points (median 2; Q1 0.5; Q3 4.5) (p < 0.001). At final visit, 46% of patients reported no pain and 38% reported a reduction of pain. At least 67% of patients had at least one episode of pain recurrence, and most patients experienced the first recurrence within a year of initial treatment. Four patients (16%) had no pain relief from the treatment. In this group of patients with CNO of the jaw, there was a positive response to treatment with zoledronic acid on pain relief, averaging 5.2 points on a pain VAS score, with 84% of patients treated experiencing either a partial or a total reduction in pain after about 2.5 years.

Evaluation of post-activation mandibular remodelling in children with craniofacial microsomia treated with distraction osteogenesis.

OBJECTIVE: Patients with type IIA craniofacial microsomia (CFM) may benefit from mandibular distraction osteogenesis (MDO) treatment during childhood; however, remodelling of the mandible during the consolidation phase, which may affect the short-term outcomes of MDO, has not yet been quantitatively analysed using computed tomography. Therefore, we aimed to investigate bone remodelling of the mandible in children with type IIA CFM treated with MDO before distractor removal and the factors that influence ramus vertical elongation efficiency. MATERIALS AND METHODS: Twenty-three children with unilateral CFM were studied between 2020 and 2024. Longitudinal computed tomography data (preoperative, end of active phase and at pre-distractor removal) were analysed. Condyle positions and the mandibular cant were analysed using a paired-sample t test. The relapse rates of vertical lengthening and mandibular cant were calculated. The correlation between distraction efficiency and preoperative craniofacial morphology was analysed. RESULTS: The condyle on the affected side moved upwards and backwards by 28.84 ± 4.08 and 2.85 ± 4.33 mm, respectively during the active phase but lost 7.66 ± 2.64 mm of vertical extension during the consolidation phase. The relapse rates for vertical extension of the condyle and occlusal plane were 27% and 35%, respectively. The ratio of mandibular ramus height was positively related to EV. CONCLUSIONS: In children with CFM, attention should be paid to vertical elongation instability and relapse of mandibular inclination during consolidation. Severe mandibular ramus hypoplasia is a preoperative risk factor for vertical skeletal relapse during consolidation. Further efforts are required to reduce the stress that leads to relapse.

Salivary levels of Osteoprotegerin and receptor activator of nuclear factor-kappa ligand during orthodontic tooth movement-A prospective pilot study.

OBJECTIVES: The aim of this study was to monitor changes in Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa ligand (RANKL) levels in the saliva during orthodontic tooth movement (OTM). MATERIALS AND METHODS: Nine healthy females (15-20 y of age) with four pre-molar extractions and fixed appliance were included. In total, 134 stimulated and 134 unstimulated saliva samples were collected: at baseline and then every 6-8 weeks at follow-up appointments during the whole orthodontic treatment. Twelve age-matched females with no active orthodontic treatment served as a control group. Saliva samples were analysed by enzyme-linked immunosorbent assay (Elisa). The mean levels of OPG and RANKL were calculated according to the different orthodontic treatment stages: alignment, space closure and finishing. A mixed model analysis was used to compare the means of treatment stages. Baseline OPG levels were compared with the control group using an independent t-test. OPG levels were measured in stimulated saliva due to low levels in unstimulated saliva. RESULTS: No significant difference was observed between baseline OPG values and the control group. OPG increased significantly at all treatment stages: alignment, space closure and finishing compared with baseline (P = 0.002, P = 0.039, P ≤ 0.001, respectively). The salivary levels of OPG increased gradually, except during space closure, reaching peak levels at finishing. RANKL was undetectable in stimulated and unstimulated saliva by sandwich Elisa during OTM. CONCLUSIONS: This novel approach shows the changes in the levels of OPG in OTM and indicates how and when to sample saliva during orthodontic treatment to analyse bone remodelling.

Small nucleolar RNA host gene 5 plays a role in orthodontic tooth movement by inhibiting osteoclast differentiation.

BACKGROUND AND OBJECTIVES: The alveolar bone remodelling promoted by reasonable mechanical force triggers orthodontic tooth movement (OTM). The generation of osteoclasts is essential in this process. However, the mechanism of mechanical force mediating osteoclast differentiation remains elusive. Small nucleolar RNA host gene 5 (SNHG5), which was reported to mediate the osteogenic differentiation of bone marrow mesenchymal stem cells in our previous study, was downregulated in human periodontal ligament cells (hPDLCs) under mechanical force. At the same time, the RANKL/OPG ratio increased. Based on this, we probed into the role of SNHG5 in osteoclast formation during OTM and the relevant mechanism. MATERIALS AND METHODS: SNHG5 and the RANKL/OPG ratio under different compressive forces were detected by western blotting (WB) and qRT-PCR. Impact of overexpression or knockdown of SNHG5 on osteoclast differentiation was detected by qRT-PCR, WB and transwell experiments. The combination of SNHG5 and C/EBPß was verified by RNA immunoprecipitation and RNA pull-down assays. The expression of SNHG5 and osteoclast markers in gingiva were analysed by qRT-PCR and the paraffin sections of periodontal tissues were used for histological analysis. RESULTS: Compressive force downregulated SNHG5 and upregulated the RANKL/OPG ratio in hPDLCs. Overexpression of SNHG5 inhibited RANKL's expression and osteoclast differentiation. SNHG5 combined with C/EBPß, a regulator of osteoclast. The expression of SNHG5 in periodontal tissue decreased during OTM. CONCLUSION: SNHG5 inhibited osteoclast differentiation during OTM, achieved by affecting RANKL secretion, which may provide a new idea to interfere with bone resorption during orthodontic treatment.

Evaluation of Bone Turnover Markers in Patients with Acute and Chronic Leukemia.

This study investigated different bone biomarkers (cross-linked carboxy-terminal telopeptide of type 1 collagen (CTX-1), pyridinoline (PYD), osteocalcin (OC), interleukin-6 receptor (IL-6R), calcium (Ca), and magnesium (Mg)) in terms of their metabolism in 4 different leukemia subtypes (ALL, AML, CLL and CML). The design was case control study with 30 controls and 60 cases of leukemia patients. Authors have reported many results regarding decrease as well as increase of specific bone biomarker under investigation with each leukemia subtype when compared to control. In addition, Authors reported correlations between each biomarker level and leukemia subtypes.

Can radiomic features extracted from intra-oral radiographs predict physiological bone remodelling around dental implants? A hypothesis-generating study.

AIM: The rate of physiological bone remodelling (PBR) occurring after implant placement has been associated with the later onset of progressive bone loss and peri-implantitis, leading to medium- and long-term implant therapy failure. It is still questionable, however, whether PBR is associated with specific bone characteristics. The aim of this study was to assess whether radiomic analysis could reveal not readily appreciable bone features useful for the prediction of PBR. MATERIALS AND METHODS: Radiomic features were extracted from the radiographs taken at implant placement (T0) using LifeX software. Because of the multi-centre design of the source study, ComBat harmonization was applied to the cohort. Different machine-learning models were trained on selected radiomic features to develop and internally validate algorithms capable of predicting high PBR. In addition, results of the algorithm were included in a multivariate analysis with other clinical variables (tissue thickness and depth of implant position) to test their independent correlation with PBR. RESULTS: Specific radiomic features extracted at T0 are associated with higher PBR around tissue-level implants after 3 months of unsubmerged healing (T1). In addition, taking advantage of machine-learning methods, a naive Bayes model was trained using radiomic features selected by fast correlation-based filter (FCBF), which showed the best performance in the prediction of PBR (AUC = 0.751, sensitivity = 66.0%, specificity = 68.4%, positive predictive value = 73.3%, negative predictive value = 60.5%). In addition, results of the whole model were included in a multivariate analysis with tissue thickness and depth of implant position, which were still found to be independently associated with PBR (p-value < .01). CONCLUSION: The combination of radiomics and machine-learning methods seems to be a promising approach for the early prediction of PBR. Such an innovative approach could be also used for the study of not readily disclosed bone characteristics, thus helping to explain not fully understood clinical phenomena. Although promising, the performance of the radiomic model should be improved in terms of specificity and sensitivity by further studies in this field.

Serum concentration of dickkopf-related protein 1 (DKK1) in psoriatic arthritis in the context of bone remodelling.

Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by the pathological occurrence of two opposite phenomena-osteoresorption and osteogenesis. Dickkopf-related protein 1 (DKK1) which inhibits the Wingless protein (Wnt) signalling pathway has been shown to be a master regulator of bone remodeling in inflammatory rheumatic diseases. However, the exact relationship between DKK1 serum level and bone remodelling is not clear. The goal of this study is to review state-of-the-art knowledge on the association of serum DKK1 with a bone remodelling in PsA. The MEDLINE-PubMed, EMBASE, Scopus, Web of Science and DOAJ databases were searched for appropriate papers. The English terms: 'DKK1', 'Dickkopf-1' 'Dickkopf related protein 1', 'psoriatic arthritis' and 'PsA' were used for search purposes. Eight original articles and two reviews were identified up to August 2023. In four out of 8 discussed studies DKK1 serum level was higher in PsA patients than in healthy controls [Dalbeth, p < 0.01; Diani, p < 0.001; Chung, p < 0.01; Abd el Hamid, p < 0.001)], it was comparable in another (Daousiss, p = 0.430) and was lower in two (Fassio2017, p < 0.05; Fassio2019, p < 0.05). In one study, the comparative groups included patients with axial spondyloarthritis, where DKK1 serum levels were lower in PsA groups [Jadon, peripheral PsA, p = 0.01]. The true relative serum concentration of DKK1 in PsA, as well as its influence on osteogenesis and osteoresorption, is still equivocal. Further studies on this matter with consistent and stringent methodology are warranted.

The role of ephrinB2-EphB4 signalling in bone remodelling during orthodontic tooth movement.

OBJECTIVE: The aim of this study was to investigate the role of ephrinB2-EphB4 signalling in alveolar bone remodelling on the tension side during orthodontic tooth movement (OTM). MATERIALS AND METHODS: An OTM model was established on sixty 8-week-old male Wistar rats. They were randomly divided into the experimental group and the control group. The animals in the experimental group were administrated with subcutaneous injection of EphB4 inhibitor NVP-BHG712 every other day, whereas the control group received only the vehicle. Samples containing the maxillary first molar and the surrounding bone were collected after 0, 3, 7, 14 and 21 days of tooth movement. RESULTS: EphrinB2-EphB4 signalling was actively expressed on the tension side during tooth movement. Micro-CT analysis showed the distance of tooth movement in the experimental group was significantly greater than that of the control group (P < .05) with significantly increased trabecular separation (Tb. Sp) and decreased trabecular number (Tb. N) from day 14 to day 21. The number of osteoclasts significantly increased in the experimental group compared with the control group after 3 and 7 days of tooth movement (P < .05). The expressions of alkaline phosphatase (ALP) and osteopontin (OPN) were significantly reduced by inhibition of EphB4 (P < .05). CONCLUSION: The inhibition of EphB4 suppressed bone formation and enhanced bone resorption activities on the tension side of tooth movement. The ephrinB2-EphB4 signalling might play an important role in alveolar bone remodelling during OTM.

Long-term morphometric changes in the anterior alveolar bone in adolescents and adults after space closure: A retrospective study.

OBJECTIVES: To analyse the morphometric changes in the anterior alveolar bone of both the maxilla and mandible after space closure and retention for 18-36 mo in adults and adolescents. MATERIALS AND METHODS: Forty-two subjects with 4 first premolars extracted followed by retracting anterior teeth were included and divided into two age groups: adult group (4 males, 17 females, mean age: 23.67 ± 5.29 y, treatment duration: 27.95 mo, retention duration: 26.96 mo, ANB: 4.8 ± 2.1, U1-L1: 117.2 ± 9.2, U1-PP: 120.2 ± 7.2, L1-MP: 99.2 ± 5.3) and adolescent group (6 males, 15 females, mean age: 11.52 ± 1.21 y, treatment duration: 26.18 mo, retention duration: 25.79 mo, ANB: 5.2 ± 2.1, U1-L1: 116.0 ± 8.6, U1-PP: 119.8 ± 4.9, L1-MP: 99.7 ± 4.9). Alveolar bone height and thickness of anterior teeth in both groups were measured using cone beam computed tomography (CBCT) imaging performed at the pretreatment (T1), posttreatment (T2) and retention phases (T3). One-way repeated-measure ANOVAs were performed to evaluate the alveolar bone changes. Voxel-based superimpositions were performed to measure the amount of tooth movement. RESULTS: After orthodontic treatment, the lingual bone height and thickness of both arches and the labial bone height of the mandible decreased significantly in both age groups (P < .05). Most of the labial bone height and thickness of the maxilla in both groups remained unchanged (P > .05). After retention, the lingual bone height and thickness increased significantly in both age groups (P < .05). The amounts of increased height ranged from 1.08 to 1.64 mm in adults and from 0.78 to 1.21 mm in adolescents, and the amounts of increased thickness ranged from 0.23 mm to 0.62 mm in adults and from 0.16 mm to 0.36 mm in adolescents. Obvious movements of the anterior teeth during retention were not found (P > .05). CONCLUSIONS: Although lingual alveolar bone loss occurred in adolescents and adults during orthodontic treatment, continuous remodelling occurred in the later retention phase, which provides a reference for clinical treatment planning of bimaxillary dentoalveolar protrusion.

Alveolar bone remodelling and stability of mandibular incisors in adult patients after orthodontic treatment with premolar extractions: A prospective follow-up study.

OBJECTIVE: To evaluate alveolar bone remodelling and stability of mandibular incisors in adult orthodontic extraction patients. MATERIALS AND METHODS: Cone-beam computed tomography images of 25 adult patients undergoing extraction were collected before orthodontic treatment (T1), after orthodontic treatment (T2), and after at least 1 year of retention (T3). The labial and lingual alveolar bone heights (ABH), thickness (ABT), and tooth movement of the mandibular incisors were measured during the retraction (T2-T1) and retention (T3-T2) periods. According to the tooth movement during the retention period, the mandibular incisors were further divided into stable and unstable groups, and the correlation between L1-BMe and stability was evaluated. RESULTS: The labial and lingual ABHs significantly increased after orthodontic treatment and decreased during the retention period. The lingual ABH was 7.36 ± 2.27 mm at T2 and 5.37 ± 1.98 mm at T3, indicating a great bone remodelling capacity. The labial ABT exhibited a significant increase during orthodontic treatment and a slight decrease during the retention period, while the lingual ABT showed an opposite trend. During the retention period, the root apex moved labially into the alveolar bone housing. L1-BMe significantly increased during orthodontic treatment and decreased during the retention period. Compared to the stable group, lingual ABH and L1-BMe at T2 was significantly higher, and lingual ABT was smaller in the unstable group. CONCLUSION: Post-treatment lingual alveolar bone defects of the mandibular incisors could recover to some extent during the retention period. There was a negative correlation between post-treatment L1-BMe and mandibular incisor stability.

Decreased serum MMP-9 levels in patients with nontraumatic osteonecrosis of the femoral head.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) are involved in the pathological mechanism of osteonecrosis of the femoral head (ONFH). This study aimed to investigate the relationship of serum MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio with disease severity in patients with nontraumatic ONFH. METHODS: Serum levels of MMP-9 and TIMP-1 among 102 nontraumatic ONFH patients and 96 healthy individuals were determined by enzyme-linked immunosorbent assay (ELISA). Imaging severity was determined using the FICAT classification system. The Harris hip score (HHS) and visual analogue scale (VAS) were used to evaluate clinical progress. The correlations of serum MMP-9 and TIMP-1 levels with imaging severity and clinical progress was evaluated statistically. The diagnostic value of MMP-9 for NONFH disease severity was evaluated by examining receiver operating characteristic (ROC) curves. RESULTS: The serum MMP-9 levels and the MMP-9/TIMP-1 ratio were significantly increased in patients with ONFH compared to normal controls, and TIMP-1 levels did not differ between the two groups. Serum MMP-9 levels and the MMP-9/TIMP-1 ratio were positively correlated with FICAT stage and VAS and were negatively correlated with the HHS score. The ROC curve results indicated that MMP-9 could be used as a potential marker of nontraumatic ONFH imaging progression. CONCLUSIONS: We hypothesize that increased MMP-9 expression and an imbalance in the MMP-9/TIMP-1 ratio play a role in the development of ONFH and are correlate with the severity of ONFH. The determination of MMP-9 can be a useful tool to assess the severity of the disease in patients with nontraumatic ONFH.

Inter-implant distance and buccal bone thickness for a novel implant design: a preclinical study.

OBJECTIVES: This study assessed bone height between novel tapered implants at different inter-implant thread peak (TP) distances, and the impact of TP distance from outer buccal bone (BB) on marginal bone levels (MBL). MATERIALS AND METHODS: Fully tapered implants with 0.5-mm thread depth and TP diameter 1 mm wider than the shoulder diameter were placed in healed ridges of minipigs. On one side, four implants were placed with inter-implant TP distances of 1, 2, or 3 mm corresponding to inter-implant implant shoulder distances of 2, 3, and 4 mm respectively. Three implants were placed on the other side with TP distances to outer BB of > 1 mm, 0.5-1 mm, or < 0.5 mm. After 12 weeks, (a) first bone-to-implant contact (fBIC), total BIC, bone area-to-total area (BATA), and coronal bone height between implants (Bi ½ max) for inter-implant distance, and (b) fBIC, BIC, and perpendicular crest to implant shoulder (pCIS) for BB were evaluated. RESULTS: No significant differences in bone healing and inter-implant bone height were noted for any of the TP distances. BB resorption was significant when TP distance to outer BB was < 0.5 mm. However, fBIC was lowest with TP to outer BB of 1.75 mm. CONCLUSIONS: Inter-implant bone height between adjacent implants can be maintained even at an inter-implant TP distance as low as 1 mm. A minimum TP to outer BB distance of 0.75 mm is required for predictable maintenance of MBL. CLINICAL RELEVANCE: Inter-implant distance and BB thickness are clinically relevant and require preclinical research to clarify concepts.

Step-back anterior repositioning splint retraction for temporomandibular joint disc displacement with reduction in adult patients.

BACKGROUND: Anterior repositioning splint (ARS) is used to treat temporomandibular joint (TMJ) disc displacement with reduction (DDwR). However, high recurrence rate remains a problem especially in patients with unstable occlusions. OBJECTIVE: This study optimised standard ARS therapy and proposed a step-back ARS retraction (SAR) method in adult patients with DDwR. METHODS: Dental examinations and magnetic resonance imaging of TMJ were obtained before treatment (T0), 1 to 3 months (T1), 3 to 6 months (T2) and 6 to 12 months (T3) during treatment in 48 adults (average age 27.1 ± 5.7 years). After 3 months of basic ARS wearing, personalised treatment for patients with normal disc-condyle relationship was prescribed depending on bilaminar zone adaptations and severity of molar openbite. SAR which required sequential ARS wearing was designed for patients with deep overbite/overjet until retrodiscal tissue adaptations and stable occlusions were achieved. RESULTS: The maximum interincisal opening was increased from 44.3 ± 6.9 to 45.3 ± 6.3 mm (p < .01), and joint pain was alleviated after ARS treatment. The overall success rate of ARS wearing was 92.1% (58/63) featured by a recaptured disc. Fifteen patients who underwent SAR therapy all showed bilaminar zone adaptations in the end, and one patient had positive condylar bone remodelling. CONCLUSIONS: ARS treatment could improve mouth opening and joint symptoms in adult DDwR patients. SAR method was suitable for treating DDwR patients with deep overbite and overjet and improved retrodiscal tissue adaptations and condylar bone remodelling.

Comparative evaluation of trabecular bone structures of bruxist and non-bruxist individuals with bone apposition in the mandible angle region by fractal analysis.

OBJECTIVE: This study aimed to compare the trabecular internal structure of different regions of the mandible according to the grades of appositional classification in the mandible angle region in probable bruxist individuals and non-bruxist G0(Convex course of the basal cortex, no directional change, no bone apposition) individuals by measuring fractal dimension (FD) on panoramic radiographs. METHODS: 200 sample jaws, bilaterally, of 80 probable bruxists and 20 non-bruxist G0 individuals were included in the study. According to the classification in the literature, each mandible angle apposition severity was classified as G0-G1-G2-G3. FD was calculated by selecting the region of interest (ROI) area of 7 regions from each sample. Gender differences in changes between ROIs in radiographs and independent samples t-test were evaluated. Relation between categorical variables was determined by chi-square test (p < .05). RESULTS: In the comparison of the probable bruxist and non-bruxist G0 groups, FD was found to be statistically significantly higher in the mandible angle (p = 0.013) and cortical bone (p = 0.000) regions in the probable bruxist group than in the non-bruxist G0 group. There is a statistically significant difference between probable bruxist G0 and non-bruxist G0 grades in terms of FD averages in cortical bone (p < 0.001). A statistically significant difference was found in the relationship of ROIs with gender in canine apex (p = 0.021) and canine distal (p = 0.041) regions. CONCLUSION: FD was found to be higher in the mandibular angle region and cortical bone in probable bruxist individuals than in non-bruxist G0 individuals. Morphological changes seen in the mandible angulus region may be a finding that may raise suspicion for bruxism for clinicians.

Stress shielding effect after total hip arthroplasty varies between combinations of stem design and stiffness-a comparing biomechanical finite element analysis.

PURPOSE: Total hip arthroplasty (THA) has become a highly frequent orthopaedic procedure. Multiple approaches have been made to design the femoral component for THA with a mechanical behaviour as close as possible to a natural femur. The aim of this study was to compare different combinations of design and biomechanical properties of THA prostheses and their impact on stress shielding of the periprosthetic bone. METHODS: Virtual implantation of different stem designs (straight standard stem, straight short stem, anatomical short stem) by finite element analysis based on in vivo data from computer tomography was performed. For each stem, three grades of stiffness were generated, followed by a strain analysis. RESULTS: Reduction of stem stiffness led to less stress shielding. Implantation of an anatomical short-stem prosthesis with low stiffness provided the most physiological strain-loading effect (p < 0.001). CONCLUSION: A combination of a short and an anatomically designed stem with a low stiffness might provide a more physiological strain transfer during THA. Biomechanical properties of the femoral component for THA should be considered as a multifactorial function of dimensions, design, and stiffness.

The Emerging Role of MMP12 in the Oral Environment.

Matrix metalloproteinase-12 (MMP12), or macrophage metalloelastase, plays important roles in extracellular matrix (ECM) component degradation. Recent reports show MMP12 has been implicated in the pathogenesis of periodontal diseases. To date, this review represents the latest comprehensive overview of MMP12 in various oral diseases, such as periodontitis, temporomandibular joint dysfunction (TMD), orthodontic tooth movement (OTM), and oral squamous cell carcinoma (OSCC). Furthermore, the current knowledge regarding the distribution of MMP12 in different tissues is also illustrated in this review. Studies have implicated the association of MMP12 expression with the pathogenesis of several representative oral diseases, including periodontitis, TMD, OSCC, OTM, and bone remodelling. Although there may be a potential role of MMP12 in oral diseases, the exact pathophysiological role of MMP12 remains to be elucidated. Understanding the cellular and molecular biology of MMP12 is essential, as MMP12 could be a potential target for developing therapeutic strategies targeting inflammatory and immunologically related oral diseases.

PIEZO1 promotes ATP release from periodontal ligament cells following compression force.

OBJECTIVES: Orthodontic mechanical force on the periodontal ligament induces extracellular adenosine triphosphate (ATP) release. However, mechanosensitive molecules have not been confirmed functionally in periodontal ligament cells. In the present study, we examined the roles of mechanosensitive PIEZO channels in the mechanically stimulated release of ATP in human periodontal ligament fibroblasts (HPdLFs). MATERIALS AND METHODS: To examine PIEZO expression in HPdLFs, we performed reverse transcription-quantitative polymerase chain reaction, fluorescent immunostaining, and Ca2+ imaging. ATP concentrations were measured in culture medium after applications of the PIEZO1 agonist Yoda1 and compression force in a newly developed in vitro weight-loaded cell model (IVWLC) using balance weights and a 48-well plate. The mechanosensitive channel inhibitor GsMTx4 and the ATP-releasing route inhibitors clodronic acid, meclofenamic acid, and probenecid were used. To suppress PIEZO1 expression, short interference RNA (siRNA) treatment of the PIEZO1 gene was performed. RESULTS: PIEZO1 mRNA was expressed more abundantly than PIEZO2 mRNA in HPdLFs. HPdLF cell bodies were immunoreactive to anti-PIEZO1 antibody. Yoda1 increased intracellular Ca2+ and extracellular ATP concentrations in a dose-dependent manner. ATP release was inhibited by GsMTx4 and inhibitors of ATP release routes. In the IVWLC, HPdLFs released ATP in response to compression force but not in response to hypoxic stimulation that was simultaneously applied to cells. Mechanically stimulated ATP release was inhibited by GsMTx4, inhibitors of ATP-releasing routes and siRNA treatment of PIEZO1. CONCLUSIONS: PIEZO1 on the cell membranes of HPdLFs is activated by compression force and then induces ATP release via intracellular Ca2+-dependent exocytosis and ATP-permeable channels.