Yunsong Liu

Increased bone marrow adiposity is a characteristic of osteoporosis and negatively regulates osteogenesis. Bone marrow mesenchymal stem cells (BMSCs) give rise to bone marrow adipocytes. The transcription factor interferon regulatory factor 1 (IRF1) modulates multiple biological processes, including the adipogenesis of several cell types. However, the role of IRF1 in the commitment of BMSCs to the adipogenic lineage and whether it regulates bone marrow adipogenesis has not been investigated thoroughly. Murine BMSCs (mBMSCs) with Irf1 ‐overexpression or knockdown were established via lentiviral transfection. IRF1's effects on adipogenic differentiation and autophagy of mBMSCs were studied in vitro; its role in adipogenesis in vivo was evaluated via nude mouse subcutaneous transplantation. Irf1 ‐overexpressing mBMSCs were intravenously injected into OVX and aged osteoporotic mice. Besides, RNA sequencing and experimental verification explored the mechanism. IRF1 inhibited the adipogenic differentiation of mBMSCs both in vitro and in vivo. Besides, IRF1 positively regulated autophagy in mBMSCs in vitro. In osteoporotic mice, injection of Irf1 ‐overexpressing mBMSCs effectively decreased bone marrow adiposity. IRF1 may downregulate adipogenic differentiation of mBMSCs by regulating the 5′‐adenosine monophosphate (AMP)‐activated protein kinase (AMPK)‐mammalian target of rapamycin (mTOR) signaling axis. This study reveals that IRF1 induces protective autophagy and inhibits adipogenic differentiation of mBMSCs. Irf1 ‐overexpressing mBMSCs alleviate osteoporosis‐related bone marrow adiposity. Besides, IRF1 possibly regulates the AMPK–mTOR signaling axis. Our findings establish IRF1 as a key factor inhibiting adipogenesis, providing a new potential therapeutic target for preventing and treating osteoporosis‐related bone marrow adiposity and other diseases with abnormal adipose metabolism.

Emerging evidence suggests that osteoarthritis (OA) progression is critically associated with disruptions of cartilage matrix homeostasis caused by mitochondrial impairment in chondrocytes. Apoptotic vesicles (apoVs) derived from mesenchymal stem cells (MSCs) have exhibited great therapeutic promising for tissue regeneration and osteoarticular diseases. However, their poor ability targeting chondrocytes and short-time retention in joint cavity hinder further clinical translation. As a chemically synthesized nucleic acid, aptamer tgg2 demonstrated a robust specificity binding with chondrocytes. In this study, our team successfully functionalized apoVs with tgg2 (tgg2@apoVs) via Schiff base reaction with high conjugation efficiency and fabricated an injectable sustained-release system based on hyaluronic acid methacryloyl (HAMA) hydrogels. tgg2@apoVs significantly promoted chondrocyte extracellular matrix synthesis and improved mitochondrial oxidative phosphorylation (OXPHOS) in vitro. The HAMA injectable hydrogels compounded with tgg2@apoVs remarkedly alleviated OA symptoms in vivo. The potential molecular mechanism of apoVs’ improvement in mitochondrial energy metabolism of chondrocytes is preliminarily investigated. Specifically, apoVs activate transcriptional factor Yin Yang 1 (YY1) to up-regulate the expression of Cox7c, a key subunit of complex IV in electron transport chain, thereby augmenting mitochondrial OXPHOS. In conclusion, the tgg2@apoVs’ sustained-release system provides a cost-effective solution for OA treatment, and the elucidation of the molecular mechanism underlying apoVs’ enhancement of chondrocyte OXPHOS offers insights for broader applications in energy metabolism–related diseases.

Quercetin is a natural flavonoid with strong antioxidant, anti-inflammatory, and osteogenic effects, showing great promise for bone regeneration. However,

The effects of neutrophil extracellular traps (NETs) on diabetes tissue regeneration are very complex. Diabetes mellitus induces the metabolic and functional changes in neutrophils, including enhanced glucose utilization and increased NETosis. This tilts the balance of the immune microenvironment toward chronic inflammation, potentially ultimately delaying tissue regeneration. The therapeutic effect of using medications alone is limited. Here, we review NET‐mediated metabolic reprogramming and antibacterial activity as well as chronic sterile inflammation. We focus on the newly developed nanomaterials targeting NETs in tissue defects. These nanomaterials are precisely regulated in space and time and can exert multiple functions as needed, including enhancing the antibacterial ability of NETs, inhibiting the generation of NETs, and removing the excessively accumulated NETs, thereby creating a metabolic and immune microenvironment that is conducive to tissue regeneration. Drug‐loaded nanomaterials can exhibit more ideal therapeutic effects. It is hoped that this will aid a full comprehension of the connection between diabetes and NETs. Additionally, the review may inspire readers who seek clinically effective treatment modalities.

Background: Tooth wear, a prevalent multifactorial condition, causes oral issues and indirect systemic risks. However, validated animal models for its clinical pathogenic factors are lacking, hindering pathogenesis study and clinical translation. To fill this gap, this study aims to develop and validate an animal model replicating graded molar wear matching clinical features. By regulating mechanical friction duration and chemical erosion intensity, we’ll create a tool for preclinical multifactorial tooth wear research. Methods: We simulated multifactorial dental tooth wear on the molars of Sprague–Dawley rats using acid etching, thermal stimulation (hot and cold), and hard food. Animal models of different degrees of molar wear were achieved by controlling the duration and superimposition of stimuli. Alveolar bones from the animal models were examined using microcomputed tomography (micro-CT) and histopathological sections to observe the occlusal surface, dental pulp, and periodontal tissues, as well as the distance between the alveolar crest and enamel–cementum junction. Results: Micro-CT results demonstrated that wear patterns consistent with clinical wear severity classifications were successfully replicated by adjusting the method and duration of stimulation. Compared with the control group (0.20 ± 0.02 mm), the distance between the cementoenamel junction and alveolar crest was significantly higher in the experimental group (0.82 ± 0.02 mm), indicating alveolar bone resorption, which is relevant to multifactorial dental tooth wear. Hematoxylin and eosin staining showed that, compared with the control group, the experimental group exhibited increased inflammation, vacuolar degeneration, dentinal calculus, and formation of reparative dentin in the pulp. The concurrent occurrence of periodontal and pulp lesions during wear aligned with the clinical presentation of wear-associated conditions. Conclusions: We successfully developed an accurate, inexpensive, easily established model of maxillary molar wear in rats. By controlling the duration and type of stimulation with hard food, hot–cold cycles, and acid etching, we quickly and efficiently constructed models with differing degrees of multifactorial tooth wear suitable for experimental studies and clinical needs.

To investigate the effect of ultrasonic scaling on the torque of implant prosthetic abutment screws and to compare the differences in torque influence between ultrasonic tips of two different materials. In this study, a total of 22 implants were selected, and two distinct primary torque values (PTV) 15 N·cm and 35 N·cm were applied to the temporary and definitive restorations mounted on each implant, respectively. Subsequently, ultrasonic scaling was performed for one minute using either a traditional metal scaling tip (metal tip) or a carbon fiber scaling tip (fiber tip), followed by measurement of the removal torque value (RTV). Paired t-tests were used to compare the torque changes in the same prosthesis before and after ultrasonic scaling (significance level α=0.05, two-tailed) to evaluate the effect of ultrasonic scaling on torque. Under the same PTV condition, paired t-tests were also conducted to compare the RTV after scaling with different tips to analyze the influence of the tip material on RTV. The RTVs in all the four groups were significantly lower than the corresponding PTVs after ultrasonic scaling (P < 0.05). At a PTV of 15 N·cm, the RTV of the fiber tip group was (14.1±1.27) N·cm, significantly higher than that of the metal tip group (12.3±1.56) N·cm, (P < 0.05). At a PTV of 35 N·cm, the RTV of the fiber tip group was (34.0±1.29) N·cm, while that of the metal tip group was (33.1±1.70) N·cm, with no statistically significant difference between the two groups (P>0.05). Ultrasonic scaling can lead to significant attenuation of torque in implant prosthetic abutment screws. Under a lower primary torque condition (15 N·cm), carbon fiber scaling tips significantly reduce torque attenuation compared with traditional metal scaling tips. However, under a higher primary torque condition (35 N·cm), no significant difference in the effect on screw torque was observed between the two tip types. These findings suggest that screw torque should be checked after clinical peri-implant maintenance to reduce the risk of screw loosening.

Skeletal aging remains poorly understood, particularly in craniofacial bones that interface closely with the central nervous system. Here, we identify a unique aging microenvironment in skull bone marrow (BM) characterized by neutrophil accumulation and elevated MMP25, which drives skull skeletal stem cell (SSC) dysfunction via NF-κB-mediated inflammation. Neutrophil-specific deletion of Mmp25 alleviates age-associated bone loss and preserves SSC regenerative capacity. We further demonstrate that cerebrospinal fluid from young mice (yCSF) rejuvenates aged SSCs, with Secreted Protein Acidic and Rich in Cysteine (SPARC) identified as a key youth-associated factor diminished in aged CSF. Mechanistically, SPARC suppresses PU.1-dependent transcription of MMP25, thereby reducing inflammation and restoring osteogenic potential in aged SSCs. These findings define a CSF-skull BM axis linking neuroimmune signaling to skeletal aging and identify the SPARC-PU.1-MMP25 pathway as a therapeutic target for craniofacial bone regeneration.

Objective: To investigate the changes in keratinized mucosa width (KMW) at posterior implant sites through implant treatment procedures. Materials and Methods: In this retrospective study, we measured the buccal KMW at three time points: immediately before implant placement (T0), before definitive prosthesis delivery (T1), and within 1 month after prosthesis delivery (T2). We analyzed changes in the KMW at the implant sites between these time points, using both submerged and non‐submerged techniques. Results: A total of 72 patients and 98 implants were included. The KMW changed significantly from T0 to T1 (1.33 mm, 95% confidence interval [CI] [1.072, 1.561], p < 0.001) and from T0 to T2 (2.17 mm, 95% CI [1.929, 2.418], p < 0.001). No statistically significant differences were found in KMW changes between submerged and non‐submerged implants from T0 to T1 ( p = 0.556) or from T0 to T2 ( p = 0.572). The height of the abutment was significantly related to the changes in KMW from T0 to T1 (−0.274 mm, 95% CI [−0.544, −0.004], p < 0.005), but implant technique, alveolar ridge preservation (ARP), and the diameter of the abutment were not ( p > 0.05). Conclusion: The KMW at posterior implant sites decreased significantly through implant treatment procedures, which were related to the height of abutment, but not to implant technique, history of ARP, or the diameter of abutment.