Alterations in epidermal stem cells within the pilosebaceous unit in atrophic acne scars.

BACKGROUND: Atrophic acne scarring is a common sequela of inflammatory acne, causing significant problems for affected patients. Although prolonged inflammation and subsequent aberrant tissue regeneration are considered the underlying pathogenesis, the role of epidermal stem cells, which are crucial to the regeneration of pilosebaceous units, remains unknown. OBJECTIVES: To examine the changes occurring in epidermal stem cells in atrophic acne scars. METHODS: Changes in collagen, elastic fibre and human leukocyte antigen (HLA)-DR expression were analysed in normal skin and inflammatory acne lesions at days 1, 3 and 7 after development. The expression of epidermal stem cell markers and proliferation markers was compared between normal skin and mature atrophic acne scar tissue. RESULTS: In acne lesions, inflammation had invaded into pilosebaceous units over time. Their normal structure had been destructed and replaced with a reduced amount of collagen and elastic fibre. Expression of stem cell markers including CD34, p63, leucine-rich repeat-containing G protein-coupled receptor (LGR)6 and LGR5, which are expressed in the interfollicular epidermis, isthmus and bulge of hair follicles, significantly decreased in atrophic acne scar tissue compared to normal skin. Epidermal proliferation was significantly reduced in scar tissue. CONCLUSIONS: These findings suggest that as inflammatory acne lesions progress, inflammation gradually infiltrates the pilosebaceous unit and affects the resident stem cells. This disruption impedes the normal regeneration of the interfollicular epidermis and adnexal structures, resulting in atrophic acne scars.

Spontaneous resolution of spinoglenoid ganglion cyst: a case series.

BACKGROUND: Spontaneous resolution of a spinoglenoid notch ganglion cyst (SGC) without surgical treatment has been rarely reported; however, we have encountered this phenomenon occasionally. Therefore, we aimed to describe a case series of consecutive patients with SGC in whom it spontaneously resolved without surgical treatment. METHODS: We retrospectively reviewed 12 patients with magnetic resonance imaging (MRI)-confirmed SGC in whom it resolved without surgical treatment between January 2011 and March 2023. We included patients without abnormally increased signal intensity or muscle atrophy due to denervation from suprascapular neuropathy on MRI. Resolution of the SGC was confirmed via MRI or ultrasound at the follow-up visit, and suprascapular neuropathy was assessed using electromyography and nerve conduction studies when needed. For functional assessments, the visual analog scale for pain and active range of motion of the shoulder were used to compare pre and postresolution follow-ups. RESULTS: Eleven men and 1 woman with a median age of 54.0 years (interquartile range [IQR] 37.0-65.3) were included in this study. The SGCs resolved spontaneously at a median of 13.2 months with an IQR of 8.2-23.0 after initial evaluation using MRI. The SGCs were multiloculated cysts with superior labrum anterior and posterior II-IX lesions, with a median diameter of 2.5 cm (IQR 2.0-2.8). The median visual analog scale for pain (pre-resolution 5.0 [IQR 4.0-7.0] vs postresolution 1.0 [IQR 0.0-1.0], P = .002) and internal rotation at the back (preresolution 8.0 [IQR 7.0-10.3] vs postresolution 7.5 [IQR 7.0-8.0], P = .034) were significantly improved after the resolution. CONCLUSIONS: Surgical treatment may not be necessary in all cases of SGC. Nonsurgical treatment may be a viable option in the absence of suprascapular nerve involvement or superior labrum anterior and posterior-related physical findings.

Supervised diagnostic classification of cognitive attributes using data augmentation.

Over recent decades, machine learning, an integral subfield of artificial intelligence, has revolutionized diverse sectors, enabling data-driven decisions with minimal human intervention. In particular, the field of educational assessment emerges as a promising area for machine learning applications, where students can be classified and diagnosed using their performance data. The objectives of Diagnostic Classification Models (DCMs), which provide a suite of methods for diagnosing students' cognitive states in relation to the mastery of necessary cognitive attributes for solving problems in a test, can be effectively addressed through machine learning techniques. However, the challenge lies in the latent nature of cognitive status, which makes it difficult to obtain labels for the training dataset. Consequently, the application of machine learning methods to DCMs often assumes smaller training sets with labels derived either from theoretical considerations or human experts. In this study, the authors propose a supervised diagnostic classification model with data augmentation (SDCM-DA). This method is designed to utilize the augmented data using a data generation model constructed by leveraging the probability of correct responses for each attribute mastery pattern derived from the expert-labeled dataset. To explore the benefits of data augmentation, a simulation study is carried out, contrasting it with classification methods that rely solely on the expert-labeled dataset for training. The findings reveal that utilizing data augmentation with the estimated probabilities of correct responses substantially enhances classification accuracy. This holds true even when the augmentation originates from a small labeled sample with occasional labeling errors, and when the tests contain lower-quality items that may inaccurately measure students' true cognitive status. Moreover, the study demonstrates that leveraging augmented data for learning can enable the successful classification of students, thereby eliminating the necessity for specifying an underlying response model.

The efficacy and safety of low- versus high-fluence fractional picosecond Nd:YAG 1064-nm laser in the treatment of acne scars: A randomized split-face comparison study.

BACKGROUND: Differences in clinical efficacy based on the fluence of fractional picosecond laser treatment for acne scars are unknown. OBJECTIVE: To compare the efficacy and safety of low-fluence versus high-fluence fractional picosecond Nd:YAG 1064-nm laser treatment in acne scar patients. METHODS: In this 12-week, investigator-blinded, randomized, split-face study, 25 patients with moderate-to-severe acne scars received three sessions of high-fluence laser treatment (1.0 J/cm2 ) on one side of their face and low-fluence (0.3 J/cm2 ) on the other side every 4 weeks. Patients were assessed using acne scar counts, the scar global assessment (SGA), and the ECCA scar grading scale every 4 weeks. The histological analysis compared the acne scars obtained before and 4 weeks after treatment. RESULTS: At their last visit, 88.00% and 92.00% of the subjects achieved >30% reduction in scar counts on the low- and high-fluence sides, respectively, without a significant difference between the two sides. On both sides, the scar counts, SGA, and ECCA score significantly improved 4 weeks after the last treatment. Although the high-fluence side showed a greater reduction in scar counts (-66.73%) than the low-fluence side (-62.13%), the two sides had no significant difference in the grading scores. The high-fluence side showed significantly more severe pain and higher side-effect scores immediately and 4 weeks after treatment. Histological analysis revealed a significantly increased collagen, elastin, and vimentin expression after treatment on the low-fluence side. CONCLUSIONS: The low-fluence setting demonstrated comparable efficacy and superior safety in treating acne scars compared with the high-fluence setting.

Dental trauma trends in emergency care:a comparative analysis before, during, and after COVID-19.

Objectives: This analysis details the characteristics of dental trauma in South Korea during the coronavirus disease 2019 (COVID-19) (DC) pandemic and compares them in patients before and after COVID-19 (BC and AC, respectively). Materials and Methods: Data were collected from medical records of patients who visited Seoul National University Bundang Hospital's Emergency Dental Care Center during three 12-month periods: BC, DC, and AC (BC from March 1, 2019 to February 29, 2020; DC from March 1, 2020 to February 28, 2021; AC from March 1, 2022 to February 28, 2023). A retrospective review was conducted to investigate patient age, sex, time of visit, cause, and diagnosis. The study included 1,544 patients: 660 BC, 374 DC, and 510 AC. Results: Significant difference in age and sex was not observed among the three periods; 1-9 years of age was the largest group (38.3% in BC, 29.6% in DC, and 27.8% in AC), and the percentage of male patients was greater than of female patients (male proportion as 63.5% in BC, 67.4% in DC, and 64.9% in AC). The number of patients generally peaked at a Saturday night in spring (for BC: May, Saturday, 18:00-19:59; for DC: March, Saturday, 18:00-19:59; for AC: April as the second most (October as the most peaked), Saturday, 20:00-21:59). The primary etiology of the dental trauma was identical in the three periods: falls, followed by sports. The most frequent diagnosis was laceration, followed by tooth avulsion and jaw fracture. Conclusion: Significant differences were not found between the characteristics and patterns of dental trauma in the BC, DC, and AC periods. However, due to the pandemic and social distancing, activities decreased and associated dental trauma-related incidents declined.

Depolymerized Chitosan-g-[Poly(MMA-co-HEMA-cl-EGDMA)] Based Nanogels for Controlled Local Release of Bupivacaine.

This study is designed to formulate and characterize chitosan-based nanogels that provide the controlled delivery of anesthetic drugs, such as bupivacaine (BPV), for effective postoperative pain management over prolonged periods of time. Drug carriers of chitosan/poly (MMA-co-HEMA-cl-EGDMA) (CsPMH) nanogels were prepared by varying the composition of comonomers such as MMA, HEMA, and redox initiator CAN. The nanogels were then characterized using FTIR, TGA, SEM, and TEM. The CsPMH nanogels showed greater encapsulation efficiencies from 43.20-91.77%. Computational studies were also conducted to evaluate the interaction between the drug and CsPMH nanoparticles. Finally, BPV-loaded nanoparticles were used to examine their in vitro release behavior. At pH 7.4, all the drug carriers displayed the "n" value around 0.7, thus the BPV release follows anomalous diffusion. Drug carrier 7 demonstrated a steady and sustained release of BPV for approximately 24 h and released about 91% of BPV, following the K-P mechanism of drug release. On the other hand, drug carrier 6 exhibited controlled release for approximately 12 h and released only 62% of BPV.

Far-Infrared Radiation to Improve Clinical Outcomes after Arthroscopic Rotator Cuff Repair: A Prospective Randomized Comparative Clinical Study.

Background: The efficacy of far-infrared radiation (FIR) after rotator cuff repair has not been demonstrated yet. The aim of this study was to evaluate the effects of postoperatively applied FIR with regard to early pain, range of motion (ROM), and tendon-to-bone healing after arthroscopic rotator cuff repair. Methods: A total of 64 consecutive patients who underwent arthroscopic rotator cuff repair with small- to medium-sized tears were enrolled in this prospective comparative study and randomly divided into an FIR group (n = 31) and a control group (n = 33). In the FIR group, FIR using a radiator device (Aladdin-H) was applied for 30 minutes per session twice daily from the first postoperative day. This application lasted for 10 weeks during the postoperative period. Clinical outcomes were assessed using a visual analog scale for pain (pVAS) at 5 weeks and ROM at 3 and 6 months postoperatively. Functional scores were evaluated at 6 months postoperatively. Healing of the repaired rotator cuff was also evaluated using ultrasonography at 3 months and magnetic resonance imaging at 6 months postoperatively. Results: In both groups, clinical and functional outcomes were improved up to 6 months compared with preoperative values. At 5 weeks and 3 months postoperatively, the average pVAS was significantly lower in the FIR group than in the control group (1.7 ± 1.0 vs. 2.8 ± 1.4; p = 0.002 at 5 weeks, 2.4 ± 1.3 vs. 3.2 ± 1.8; p = 0.041 at 3 months). However, there was no significant difference in ROM, functional score, or healing rate between two groups at each follow-up time point. Conclusions: The application of FIR after arthroscopic rotator cuff repair could be a safe and effective procedure to decrease postoperative pain, especially in the early postoperative period. This effective application of FIR can be considered to facilitate painless rehabilitation in the postoperative period after arthroscopic rotator cuff repair.

What is the most predictive magnetic resonance imaging finding of rotator cuff tear concomitant with shoulder stiffness?

Background: Common magnetic resonance imaging (MRI) findings in adhesive capsulitis are not often evident in rotator cuff tear concomitant with shoulder stiffness. This study aimed to determine the most predictive MRI finding of rotator cuff tear with shoulder stiffness to differentiate from that without stiffness. Materials and methods: The data of patients who underwent arthroscopic rotator cuff repair between January 2014 and October 2019 were retrospectively reviewed. Stiffness was defined as forward flexion <120°, external rotation at side <30°, and internal rotation at back 

Cyclic Stretch Promotes Cellular Reprogramming Process through Cytoskeletal-Nuclear Mechano-Coupling and Epigenetic Modification.

Advancing the technologies for cellular reprogramming with high efficiency has significant impact on regenerative therapy, disease modeling, and drug discovery. Biophysical cues can tune the cell fate, yet the precise role of external physical forces during reprogramming remains elusive. Here the authors show that temporal cyclic-stretching of fibroblasts significantly enhances the efficiency of induced pluripotent stem cell (iPSC) production. Generated iPSCs are proven to express pluripotency markers and exhibit in vivo functionality. Bulk RNA-sequencing reveales that cyclic-stretching enhances biological characteristics required for pluripotency acquisition, including increased cell division and mesenchymal-epithelial transition. Of note, cyclic-stretching activates key mechanosensitive molecules (integrins, perinuclear actins, nesprin-2, and YAP), across the cytoskeletal-to-nuclear space. Furthermore, stretch-mediated cytoskeletal-nuclear mechano-coupling leads to altered epigenetic modifications, mainly downregulation in H3K9 methylation, and its global gene occupancy change, as revealed by genome-wide ChIP-sequencing and pharmacological inhibition tests. Single cell RNA-sequencing further identifies subcluster of mechano-responsive iPSCs and key epigenetic modifier in stretched cells. Collectively, cyclic-stretching activates iPSC reprogramming through mechanotransduction process and epigenetic changes accompanied by altered occupancy of mechanosensitive genes. This study highlights the strong link between external physical forces with subsequent mechanotransduction process and the epigenetic changes with expression of related genes in cellular reprogramming, holding substantial implications in the field of cell biology, tissue engineering, and regenerative medicine.

Sensor development for multiple simultaneous classifications using genetically engineered M13 bacteriophages.

Sensors for detecting infinitesimal amounts of chemicals in air have been widely developed because they can identify the origin of chemicals. These sensing technologies are also used to determine the variety and freshness of fresh food and detect explosives, hazardous chemicals, environmental hormones, and diseases using exhaled gases. However, there is still a need to rapidly develop portable and highly sensitive sensors that respond to complex environments. Here, we show an efficient method for optimising an M13 bacteriophage-based multi-array colourimetric sensor for multiple simultaneous classifications. Apples, which are difficult to classify due to many varieties in distribution, were selected for classifying targets. M13 was adopted to fabricate a multi-array colourimetric sensor using the self-templating process since a chemical property of major coat protein p8 consisting of the M13 body can be manipulated by genetic engineering to respond to various target substances. The twenty sensor units, which consisted of different types of manipulated M13, exhibited colour changes because of the change of photonic crystal-like nanostructure when they were exposed to target substances associated with apples. The classification success rate of the optimal sensor combinations was achieved with high accuracy for the apple variety (100%), four standard fragrances (100%), and aging (84.5%) simultaneously. We expect that this optimisation technique can be used for rapid sensor development capable of multiple simultaneous classifications in various fields, such as medical diagnosis, hazardous environment monitoring, and the food industry, where sensors need to be developed in response to complex environments consisting of various targets.

Comparison of Posttreatment Stability Between Mandibular Setback Surgery-Early and Conventional Surgery in Class III Patients: A 4.6-Year Follow-Up.

OBJECTIVES: This retrospective study aims to compare long-term stability between the mandibular setback surgery-early (MSE) approach, involving minimal orthodontics, and the mandibular setback conventional surgery (MCS) approach, involving sufficient orthodontics, in Class III patients with mandibular prognathism. METHODS: Among 210 patients who underwent orthognathic surgery, a total of 40 subjects were enrolled based on standardized inclusion criteria: only mandibular surgery, <5 mm setback difference between right and left of the mandible, orthodontics with fixed appliances, and more than 2 years of follow-up after treatment. These patients were allocated to the MSE (n = 20) and MCS groups (n = 20) according to the duration of presurgical orthodontics. Changes in cephalometric measurements were compared between the MSE and MCS groups before surgery (T0), 1 month after surgery (T1), at the end of treatment (T2), and posttreatment retention (T3). RESULTS: The MSE and MCS groups had a mean presurgical orthodontic duration of 2 and 9.5 months, respectively. From T1 to T2, the MSE group showed a significantly larger forward movement of the mandible than the MCS group (2.1 versus 0.7 mm; P < 0.001). In addition, from T2 to T3 (average 4.6 years), the MSE group presented anterior relapse of 0.6 mm in the mandible, but there were no statistically significant intergroup differences. CONCLUSION: Although the MSE group showed greater postsurgical forward mandibular relapse than the MCS group, the two groups exhibited similar skeletal and dental stability during the posttreatment retention.

Lidocaine intensifies the anti-osteogenic effect on inflammation-induced human dental pulp stem cells via mitogen-activated protein kinase inhibition.

Background/purpose: Human dental pulp stem cells (hDPSCs) are an emerging source of mesenchymal stem cells (MSCs) for bone tissue regeneration and engineering. In bone regeneration using transplanted MSCs, the extracellular environment or co-injected drugs can affect their success or failure. In this study, we investigated the effects and signaling mechanisms of lidocaine on osteogenic differentiation of hDPSCs after inducing inflammatory conditions with lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-α). Materials and methods: To investigate the effect of lidocaine on the osteogenic differentiation of LPS/TNF-α-treated hDPSCs, alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were conducted. The expression of osteogenesis-related genes was assessed using quantitative real-time polymerase chain reaction and western blotting. The expression of mitogen-activated protein kinases was analyzed to evaluate the effect of lidocaine on osteogenic differentiation of LPS/TNF-α-treated hDPSCs. Results: Various concentrations of lidocaine (0.05, 0.2, and 1 mM) further decreased ALP and ARS staining of LPS/TNF-α-treated hDPSCs. Similarly, the mRNA and protein expression of osteogenesis-related genes was suppressed via lidocaine treatment in LPS/TNF-α-treated hDPSCs. Lidocaine treatment downregulated the protein expression of p-ERK and p-JNK in LPS/TNF-α-treated hDPSCs. Conclusion: Lidocaine intensified the inhibition of osteogenic differentiation on inflammation-induced hDPSCs by inhibiting the ERK and JNK signaling pathways. This in vitro study suggested that lidocaine may have an inhibitory effect on bone regeneration.

Ketamine-propofol (ketofol) in procedural sedation: a narrative review.

Sedation methods for dental treatment are increasingly explored. Recently, ketofol, which is a combination of ketamine and propofol, has been increasingly used because the advantages and disadvantages of propofol and ketamine complement each other and increase their effectiveness. In this review, we discuss the pharmacology of ketamine and propofol, use of ketofol in various clinical situations, and differences in efficacy between ketofol and other sedatives.

Comparison of postoperative nausea and vomiting between Remimazolam and Propofol in Patients undergoing oral and maxillofacial surgery: a prospective Randomized Controlled Trial.

BACKGROUND: Remimazolam is a recently approved, ultra-short-acting benzodiazepine. However, few studies have investigated remimazolam in relation to postoperative nausea and vomiting (PONV). This study aimed to compare the effects of remimazolam and propofol on PONV in patients undergoing oral and maxillofacial surgery. METHODS: Patients (n = 206) aged 19-65 years who were scheduled for oral and maxillofacial surgery were randomized into two groups, the remimazolam (R) and propofol group (P). In the R group (n = 94), remimazolam was used to induce anesthesia at 12 mg/kg/h and to maintain anesthesia at 1-2 mg/kg/h. In the P group (n = 95), anesthesia was induced and maintained with propofol (target effect-site concentration: 3-5 µg/ml). In both groups, remifentanil was administered at a target effect-site concentration of 2.5-4 ng/ml. The primary outcome was the overall incidence of PONV during the first 24 h after surgery. Secondary outcomes included the severity of nausea, use of rescue antiemetics, severity of postoperative pain, use of rescue analgesia, and quality of recovery. RESULTS: The incidence of PONV during the first 24 h after surgery was 11.7% and 10.5% in the R group and P group, respectively, and there was no significant difference in the severity of nausea (P > 0.05). Ten patients in the R group and ten patients in the P group required rescue antiemetics during the first 24 h after surgery (P = 0.98). No inter-group differences were observed in terms of postoperative pain score, use of rescue analgesia, and quality of recovery (P > 0.05). CONCLUSIONS: In this study, remimazolam did not increase the incidence and severity of PONV compared with propofol. TRIAL REGISTRATION: KCT0006965, Clinical Research Information Service (CRIS), Republic of Korea. Registration date: 26/01/2022.

Lidocaine inhibits osteogenic differentiation of human dental pulp stem cells in vitro.

OBJECTIVE: Lidocaine is an amide local anaesthetic commonly used for pain control, however, few studies have investigated the effect of lidocaine on the osteogenic differentiation of human dental pulp stem cells (HDPSCs). The present study aimed to determine the effect of lidocaine on HDPSC viability and osteogenic differentiation. METHODS: HDPSCs were incubated with 0, 0.05, 0.2, 0.5, and 1 mM lidocaine for 24, 48 and 72 h, after which, MTT assays were performed. HDPSCs cultured with the above lidocaine concentrations and osteogenic differentiation medium for 7 and 14 days were stained for alkaline phosphatase (ALP). Protein and mRNA levels of relevant osteogenic factors (bone morphogenetic protein-2 [BMP-2] and runt-related transcription factor 2 [RUNX2]) were examined using western blotting and real-time reverse-transcription polymerase chain reaction, respectively. RESULTS: Lidocaine did not affect the viability of HDPSCs, however, lidocaine reduced ALP activity in HDPSCs. Levels of ALP, BMP-2, and RUNX2 mRNA were reduced with lidocaine, and levels of BMP-2 and RUNX2 proteins were decreased, versus controls. CONCLUSIONS: Lidocaine inhibits osteogenic differentiation markers in HDPSCs in vitro, even at low concentrations, without cytotoxicity. This study suggests that lidocaine may inhibit osteogenic differentiation in HDPSC-mediated regenerative medicine, including pulp regeneration and repair.

The Potential Application of Human Gingival Fibroblast-Conditioned Media in Pulp Regeneration: An In Vitro Study.

Regenerative endodontic treatment based on tissue engineering has recently gained interest in contemporary restorative dentistry. However, low survival rates and poor potential differentiation of stem cells could undermine the success rate of pulp regenerative therapy. Human gingival fibroblast-conditioned medium (hGF-CM) has been considered a potential therapy for tissue regeneration due to its stability in maintaining multiple factors essential for tissue regeneration compared to live cell transplantation. This study aimed to investigate the potency of hGF-CM on stem cells from human dental pulp (DPSC) in pulp regeneration. A series of experiments confirmed that hGF-CM contributes to a significant increase in proliferation, migration capability, and cell viability of DPSC after H2O2 exposure. Moreover, it has been proved to facilitate the odontogenic differentiation of DPSC via qRT-PCR, ALP (alkaline phosphatase), and ARS (Alizarin Red S) staining. It has been discovered that such highly upregulated odontogenesis is related to certain types of ECM proteins (collagen and laminin) from hGF-CM via proteomics. In addition, it is found that the ERK pathway is a key mechanism via inhibition assay based on RNA-seq result. These findings demonstrate that hGF-CM could be beneficial biomolecules for pulp regeneration.

Propofol protects against lipopolysaccharide-induced inflammatory response in human amnion-derived WISH cells.

Background: Nonobstetric surgery is sometimes required during pregnancy, and neck abscess or facial bone fracture surgery cannot be postponed in pregnant women. However, dental surgery can be stressful and can cause inflammation, and the inflammatory response is a well-known major cause of preterm labor. Propofol is an intravenous anesthetic commonly used for general anesthesia and sedation. Studies investigating the effect of propofol on human amnion are rare. The current study investigated the effects of propofol on lipopolysaccharide (LPS)-induced inflammatory responses in human amnion-derived WISH cells. Methods: WISH cells were exposed to LPS for 24 h and co-treated with various concentrations of propofol (0.01-1 µg/ml). Cell viability was measured using the MTT assay. Nitric oxide (NO) production was analyzed using a microassay based on the Griess reaction. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE 2), p38, and phospho-p38 was analyzed using western blotting. Results: Propofol did not affect the viability and NO production of WISH cells. Co-treatment with LPS and propofol reduced COX-2 and PGE2 protein expression and inhibited p38 phosphorylation in WISH cells. Conclusion: Propofol does not affect the viability of WISH cells and inhibits LPS-induced expression of inflammatory factors. The inhibitory effect of propofol on inflammatory factor expression is likely mediated by the inhibition of p38 activation.

Propofol attenuates odontogenic/osteogenic differentiation of human dental pulp stem cells in vitro.

Background/purpose: Various studies have used stem cells in the field of bone tissue engineering to repair bone defects. Dental pulp stem cells (DPSCs) have multipotent properties and can be acquired in a noninvasive manner; therefore, they are frequently used in experiments in regenerative medicine. The objective of this study was to investigate the odontogenic/osteogenic differentiation of human DPSCs (hDPSCs) using propofol, a widely used intravenous anesthetic agent. Materials and methods: Alkaline phosphatase (ALP) staining was used to investigate the effects of various concentrations of propofol (5, 20, 50 and 100 µM) on the osteogenic differentiation of hDPSCs. Real-time qPCR and Western blot analysis were used to detect the effect of propofol on the expression of odontogenic/osteogenic genes, such as DMP1, RUNX2, OCN, and BMP2. Odontogenic/osteogenic differentiation of hDPSCs was estimated at days 7 and 14. Results: ALP staining of hDPSCs was significantly decreased by propofol treatment. The mRNA expression of DMP1, RUNX2, OCN, and BMP2 decreased after propofol treatment for 14 days. The protein expression of DMP1 and BMP2 was decreased by propofol at days 7 and 14, and that of RUNX2 was decreased by propofol at day 14 only. Conclusion: Propofol attenuated odontogenic/osteogenic differentiation of hDPSCs in vitro. This result suggests that propofol, which is widely used for dental sedation, may inhibit the odontogenic/osteogenic differentiation of hDPSCs.

Chemically-induced osteogenic cells for bone tissue engineering and disease modeling.

Cell reprogramming can satisfy the demands of obtaining specific cell types for applications such as tissue regeneration and disease modeling. Here we report the reprogramming of human fibroblasts to produce chemically-induced osteogenic cells (ciOG), and explore the potential uses of ciOG in bone repair and disease treatment. A chemical cocktail of RepSox, forskolin, and phenamil was used for osteogenic induction of fibroblasts by activation of RUNX2 expression. Following a maturation, the cells differentiated toward an osteoblast phenotype that produced mineralized nodules. Bulk and single-cell RNA sequencing identified a distinct ciOG population. ciOG formed mineralized tissue in an ectopic site of immunodeficiency mice, unlike the original fibroblasts. Osteogenic reprogramming was modulated under engineered culture substrates. When generated on a nanofiber substrate ciOG accelerated bone matrix formation in a calvarial defect, indicating that the engineered biomaterial promotes the osteogenic capacity of ciOG in vivo. Furthermore, the ciOG platform recapitulated the genetic bone diseases Proteus syndrome and osteogenesis imperfecta, allowing candidate drug testing. The reprogramming of human fibroblasts into osteogenic cells with a chemical cocktail thus provides a source of specialized cells for use in bone tissue engineering and disease modeling.