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It is well established that UV radiation can inactivate bacteria by destroying DNA in the cell envelope, and maintaining the integrity of the cellular membrane. However, how UV radiation changes the surface properties and thus affects bacterial adhesion remain elusive. In this study, single‐cell force spectroscopy is employed to examine the surface nanomechanics of Pseudomonas aeruginosa under UV exposure. It shows that P. aeruginosa became stiffer after UV radiation, and its adhesion to silicon surface decreases with rupture length increasing. Nanospring signatures in the retraction force curve become less with lower spring constant but more plateau signatures with higher rupture length appear. These facts indicate the unfolding of the α‐helices of the pili. Besides, the worm‐like chain force curves with higher contour length indicate the structural degradation of transmembrane proteins or surface macromolecules obstruction. Accordingly, the bacterial adhesion decreases after UV radiation. [ABSTRACT FROM AUTHOR]

Periodontal ligament stem cells (PDLSCs) are considered ideal cell sources for the regeneration of periodontal and alveolar bone tissue. Cytoskeleton Regulator RNA (CYTOR), a newly discovered long noncoding RNA, has been reported to function as competing endogenous RNA (ceRNA) and to be involved in many biological processes. However, its roles in PDLSC osteogenic differentiation remain unclear. Here, we firstly found CYTOR was mainly sublocalized in the cytoplasm of PDLSCs and CYTOR expression was increased during osteogenic differentiation of PDLSCs. By employing gain- and loss-of-function approaches, we then identified CYTOR overexpression promoted osteogenic differentiation of PDLSCs while CYTOR knockdown inhibited this process. Furthermore, bioinformatics analysis was utilized to show that both CYTOR and SOX11 mRNA contained the same seed sites for miR-6512-3p, which was further confirmed by dual luciferase reporter assay and RNA-binding protein immunoprecipitation. Notably, CYTOR conferred its functions by directly binding to miR-6512-3p and an inverse correlation between CYTOR and miR-6512-3p on the level on SOX11 and osteogenic differentiation of PDLSCs was obtained. Additionally, miR-6512-3p could bind to SOX11 mRNA 3 ′ UTR and repressed SOX11 expression. Moreover, level of SOX11 was significantly increased during osteogenic differentiation of PDLSCs. Knockdown of SOX11 attenuated the increasing effect of CYTOR overexpression on osteogenic differentiation of PDLSCs. Collectively, these data supported that CYTOR positively modulated the expression of SOX11 through competitively binding to miR-6512-3p, thus promoting osteogenic differentiation of PDLSCs. The CYTOR/miR-6512-3p/SOX11 axis could be a novel therapeutic target for periodontal regeneration medicine. [ABSTRACT FROM AUTHOR]

Nervous system is critically involved in bone homeostasis and osteogenesis. Dopamine, a pivotal neurotransmitter, plays a crucial role in sympathetic regulation, hormone secretion, immune activation, and blood pressure regulation. However, the role of dopamine on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) remains poorly understood. In this study, we firstly investigated the effect of dopamine on the apoptosis, proliferation, and osteogenic differentiation of rBMSCs. Dopamine did not, however, interfere with the apoptosis and proliferation of rBMSCs. Interestingly, dopamine suppressed the osteogenic differentiation of rBMSCs, as characterized by reduced ALP staining, ALP activity, mineralized nodule formation, and the mRNA and protein levels of osteogenesis-related genes (Col1a1, Alp, Runx2, Opn, and Ocn). Furthermore, dopamine inactivated AKT/GSK-3β/β-catenin signaling pathway. Treatment of LiCl (GSK-3β inhibitor) rescued the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. LY294002 (AKT inhibitor) administration exacerbated the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. Taken together, these findings indicate that dopamine suppresses osteogenic differentiation of rBMSCs via AKT/GSK-3β/β-catenin signaling pathway. Our study provides new insights into the role of neurotransmitters in bone homeostasis. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) have been widely demonstrated to interact with multiple cellular signaling pathways and to participate in a wide range of physiological processes. Estradiol-17β (E2) is the most potent and prevalent endogenous estrogen that plays a vital role in promoting bone formation and reducing bone resorption. Currently, little is known about the regulation of miRNAs in E2-induced osteogenic differentiation. In the present study, the primary bone marrow mesenchymal stem cells from rats (rBMSCs) were isolated and incubated with E2, followed by miRNA profiling. The microarray showed that 29 miRNAs were differentially expressed in response to E2 stimulation. Further verification by real-time reverse-transcriptase polymerase chain reaction revealed that E2 enhanced the expression of let-7b and miR-25 but suppressed the miR-30b expression. Moreover, a gain-of-function experiment confirmed that miR-30b negatively regulated the E2-induced osteogenic differentiation. These data suggest an important role of miRNAs in osteogenic differentiation. [ABSTRACT FROM AUTHOR]

Background: Fluid shear stress (FSS) is a major type of mechanical stress that is loaded on human periodontal ligament cells (hPDLCs) during mastication and orthodontic tooth movement. This study aims to clarify the effect of FSS on the osteogenic differentiation of hPDLCs and to further verify the involvement of mitogen-activated protein kinase (MAPK) signaling in this process. Methods: After isolation and characterization, hPDLCs were subjected to 2-hour FSS at 12 dynes/cm², and cell viability, osteogenic gene mRNA expression, alkaline phosphatase (ALP) activity, secretion of Type I collagen (COL-1), and calcium deposition were assayed. The levels of phosphorylated p38 and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) in response to FSS were detected by Western blot, and the involvement of ERK1/2 and p38 MAPK signaling pathways in hPDLC osteogenesis under FSS was investigated using the specific MAPK inhibitors (10126 (2Z,3Z)-2,3-bis[amino (2-aminophenylthio)methylene]succinonitrile,ethanol) and SB203580 (4-[4-(4-fluorophenyl)-2-(4-[methylsulfinyl]phenyl)-l H-imidazol-5-yl]pyridine). Results: The application of FSS on hPDLCs induced an early morphologic change and rearrangement of filamentous actin. ALP activity, messenger RNA (mRNA) levels of osteogenic genes, COL-1, and osteoid nodules were significantly increased by FSS. Moreover, ERK1/2 and p38 were activated in different ways after FSS exposure. (10126 and SB203580 completely blocked the FSS-induced increases in ALP activity and osteogenic gene mRNA expression and osteoid nodules formation. Conclusions: FSS is an effective approach for stimulating osteogenic differentiation of hPDLCs. The ERK1/2 and p38 MAPK signaling pathways are involved in this cellular process. [ABSTRACT FROM AUTHOR]

Fluid shear stress plays an important role in bone osteogenic differentiation. It is traditionally believed that pulsed and continuous stress load is more favorable for fracture recovery and bone homeostasis. However, according to our clinical practice, we notice that one single stress load is also sufficient to trigger osteogenic differentiation. In the present study, we subject osteoblast MC3T3-E1 cells to single bout short duration fluid shear stress by using a parallel plate flow system. The results show that 1 hour of fluid shear stress at 12 dyn/cm2 promotes terminal osteogenic differentiation, including rearrangement of F-actin stress fiber, up-regulation of osteogenic genes expression, elevation of alkaline phosphatase activity, secretion of type I collagen and osteoid nodule formation. Moreover, collaboration of BMP2 and integrin β1 pathways plays a significant role in such differentiation processes. Our findings provide further experimental evidence to support the notion that single bout short duration fluid shear stress can promote osteogenic differentiation. [ABSTRACT FROM AUTHOR]

• E2 with CCS has different effects on MCCs proliferation and differentiation. • E2 at physiological concentration with CCS has synergistic effect. • E2 at non-physiological concentration with CCS has no synergistic effect. The aim of this study is to investigate the effects of 17β-Estradiol (E2) at different concentrations combined with cyclical compressive stress on the proliferation and differentiation of mandibular condylar chondrocytes (MCCs). MCCs, isolated from female Sprague-Dawley rats, were exposed to E2 at different concentration, cyclical compressive stress or the combination, effects of which on MCCs proliferation and differentiation were detected. E2 at physiological concentration (10−9 mol/L) has lower proliferative effects on MCCs, compared with non-physiological concentration (10-12 mol/L or 10-6 mol/L). For MCCs differentiation, effects of E2 at different concentration are totally opposite: E2 at 10−9 mol/L promotes MCCs differentiation, but at 10-12 mol/L or 10-6 mol/L, it inhibits MCCs differentiation. When combined with E2 at 10−9 mol/L, cyclical compressive stress shows synergistic effect on proliferation and differentiation. However, when combined with E2 at 10-12 mol/L or 10-6 mol/L cyclical compressive stress reverses the inhibition in MCCs differentiation provoked by E2 at 10-12 mol/L or 10-6 mol/L. Effects of E2 combined with cyclical compressive stress on MCCs proliferation and differentiation are different, which suggests that orthodontist should take fully consideration of the levels of E2 and adopt comprehensive strategies, so as to achieve better orthodontic effect. [ABSTRACT FROM AUTHOR]

Background: Skeletal Class II malocclusion is a common malocclusion that seriously affects patients' profile and occlusal function. The key to treatment is to use functional appliances guide the mandible forward. This study aimed to evaluate the clinical efficacy of traditional functional appliance Twin Block (TB) and invisible functional appliance (A6)., Methods: In the retrospective cohort study, 46 patients with Class II Division 1 mandibular retrognathia (23 females, 23 males; mean age 13.66±4.25 years) from the Third Affiliated Hospital of Sun Yat-sen University were selected. They were divided into A6 group and TB group according to the type of appliance guided mandibular forward used in orthodontic treatment (n=23 each; average treatment time 9.82±3.52 months). Lateral cephalometric radiographs were taken before and at the end of each treatment, and paired t -test or paired rank-sum tests were performed when appropriate to detect any statistical significance at the level of α=0.05., Results: The baseline characteristics of the two groups of patients were similar. Treatment with both appliances helped correct Class II malocclusion, improve the discrepancy between the maxilla and mandible, reduce the labial inclination of the maxillary anterior teeth, and relieve the deep overbite. A comparison of the treatment effects of the TB and A6 groups showed that the A6 had a better effect when moving Point A backward, and performed better in the abduction of the anterior teeth. TB group has more advantages than A6 group in moving forward point B and improving the nasolabial angle., Conclusions: Both the A6 and TB can significantly improve Class II malocclusion. A6 showed an obvious advantage in moving Point A backward and adducting the anterior teeth, which better corrects a skeletal Class II malocclusion., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3762/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Nervous system is critically involved in bone homeostasis and osteogenesis. Dopamine, a pivotal neurotransmitter, plays a crucial role in sympathetic regulation, hormone secretion, immune activation, and blood pressure regulation. However, the role of dopamine on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) remains poorly understood. In this study, we firstly investigated the effect of dopamine on the apoptosis, proliferation, and osteogenic differentiation of rBMSCs. Dopamine did not, however, interfere with the apoptosis and proliferation of rBMSCs. Interestingly, dopamine suppressed the osteogenic differentiation of rBMSCs, as characterized by reduced ALP staining, ALP activity, mineralized nodule formation, and the mRNA and protein levels of osteogenesis-related genes ( Col1a1 , Alp , Runx2 , Opn , and Ocn ). Furthermore, dopamine inactivated AKT/GSK-3 β / β -catenin signaling pathway. Treatment of LiCl (GSK-3 β inhibitor) rescued the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. LY294002 (AKT inhibitor) administration exacerbated the inhibitory effects of dopamine on osteogenic differentiation of rBMSCs. Taken together, these findings indicate that dopamine suppresses osteogenic differentiation of rBMSCs via AKT/GSK-3 β / β -catenin signaling pathway. Our study provides new insights into the role of neurotransmitters in bone homeostasis., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Zhili Kuang et al.)

Background: MicroRNAs (miRNAs) are crucial regulators of diverse biological and pathological processes. This study aimed to investigate the role of microRNA 20a (miR-20a) in fluid shear stress (FSS)-mediated osteogenic differentiation., Methods: In the present study, we subjected osteoblast MC3T3-E1 cells or mouse bone marrow stromal cells (BMSCs) to single bout short duration FSS (12 dyn/cm 2 for 1 hour) using a parallel plate flow system. The expression of miR-20a was quantified by miRNA array profiling and real-time quantitative polymerase chain reaction (qRT-PCR) during FSS-mediated osteogenic differentiation. The expression of osteogenic differentiation markers such as Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and SP7 transcription factor (SP7) was detected. Bioinformatics analysis and a luciferase assay were performed to confirm the potential targets of miR-20a., Results: Osteoblast-expressed miR-20a is sensitive to the mechanical environments of FSS, which are differentially up-regulated during steady FSS-mediated osteogenic differentiation. MiR-20a enhances FSS-induced osteoblast differentiation by activating the bone morphogenetic protein 2 (BMP2) signaling pathway. Both BMP and activin membrane-bound inhibitor (BAMBI) and mothers against decapentaplegic family member 6 (SMAD6) are targets of miR-20a that negatively regulate the BMP2 signaling pathway., Conclusions: MiR-20a is a novel mechanosensitive miRNA that can enhance osteoblast differentiation in FSS mechanical environments, implying that this miRNA might be a target for bone tissue engineering and orthodontic bone remodeling for regenerative medicine applications., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-2753/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Purpose: This study evaluated the distance from the posterior root apices to the maxillary sinus floor (MSF) and the frequency of roots touching or protruding through the MSF using cone-beam computed tomography (CBCT)., Materials and Methods: This study included 100 subjects divided into different vertical and anteroposterior skeletal growth patterns. On CBCT images, the distance from the posterior root apices to MSF was measured and the frequency of roots touching or protruding through the MSF was evaluated using NNT software (version 5.3.0.0; ImageWorks, Elmsford, NY, USA)., Results: No statistically significant differences were found in the distance from the posterior root apices to the MSF among vertical skeletal groups ( P >0.05). The palatal roots of the first molar and the palatal, mesio-buccal and disto-buccal roots of the second molars had significantly less distance from MSF in skeletal class II than in class III ( P <0.05). The high-angle group had the highest frequencies of roots touching or protruding into the maxillary sinus (49.8%); the lowest proportion of these roots was found in skeletal class III (28.3%) and the highest proportion in class II (50.3%). Males had shorter distances from the posterior root apices to the MSF and higher frequencies of roots protruding through or touching the MSF than females., Conclusion: Anteroposterior skeletal growth patterns and sex affected the distances from the maxillary posterior roots to the MSF. The frequency of roots protruding into or touching the sinus was affected by both vertical and anteroposterior skeletal groups and sex. These findings have implications for dental practice., Competing Interests: Conflicts of Interest: None, (Copyright © 2022 by Korean Academy of Oral and Maxillofacial Radiology.)

The role of myosin light chain II (MLC‑II) in cellular differentiation of rat mandibular condylar chondrocytes (MCCs) induced by cyclical uniaxial compressive stress (CUCS) remains unclear. In the current study, a four‑point bending system was used to apply CUCS to primary cultured MCCs from rats. It was identified that CUCS stimulated features of cellular differentiation including morphological alterations, cytoskeleton rearrangement and overproduction of proteoglycans. Furthermore, CUCS promoted runt‑related transcription factor‑2 (RUNX2) expression at mRNA (P<0.01) and protein levels (P<0.05) and elevated alkaline phosphatase (ALP) activity (P<0.01), which are both markers of osteogenic differentiation. Under conditions of stress, western blotting indicated that the ratio of phosphorylated MLC‑II to total MLC‑II was increased significantly (P<0.05). Silencing MLC‑II by RNA interference reduced ALP activity (P<0.01), and eliminated RUNX2 mRNA expression (P<0.01). Addition of the MLC kinase inhibitor, ML‑7, reduced the CUCS‑associated upregulation of RUNX2 expression (P<0.01) and ALP activity (P<0.01). The data indicated that CUCS promoted cellular differentiation of rat primary MCCs, and this was suggested to be via the phosphorylation of MLC‑II.