Ruiye Bi

The Notch signaling pathway is pivotal in joint homeostasis and the pathogenesis of osteoarthritis (OA). Under physiological conditions, transient or physiological Notch signaling maintains cartilage matrix synthesis to preserve joint function. Under pathological conditions, persistent or excessive activation of Notch signaling suppresses the expression of chondrogenic genes and induces the production of catabolic factors, thereby driving OA progression. From a cellular perspective, the Notch signaling pathway exerts crucial regulatory role in the functions of various resident cell types within the joint. For instance, it regulates the differentiation and maturation of chondrocytes, influences the chondrogenic differentiation process of mesenchymal stem cells (MSCs), and modulates the phenotype of fibroblast-like synoviocytes (FLSs). At the level of the extracellular cartilage microenvironment, the Notch signaling pathway participates in extracellular matrix (ECM) homeostasis imbalance and inflammatory factor activation in OA by regulating the expression of downstream genes. Furthermore, Notch controls chondrocyte hypertrophic degeneration through extensive molecular crosstalk with the TGF-β/BMP, Wnt/β-catenin, NF-κB, and Hippo-YAP pathways. Beyond cartilage, Notch plays a crucial role in promoting neurovascular invasion at the osteochondral junction and abnormal subchondral bone remodeling, which directly contributes to joint pain and structural failure. Many Notch-targeted approaches, such as pharmacological inhibitors, RNA-based therapies, and molecular interventions targeting ligands and downstream effectors, have been investigated because existing treatments are unable to stop the progression of OA. Simultaneously, stem cell-based approaches use precise Notch modulation to improve cartilage repair and chondrogenic differentiation. However, systemic administration of small-molecule inhibitors raises concerns about off-target effects and delivery inefficiency in avascular cartilage, while conventional stem cell injections frequently encounter problems like phenotypic instability and limited durability. In conclusion, in-depth studies on the Notch signaling pathway in OA not only clarify the pathogenesis of OA but also lay a theoretical and experimental foundation for the development of innovative therapeutic strategies.

This review aims to provide an updated overview of the genetic etiology of mandibular prognathism (MP), focusing on recent research efforts, to summarize the findings from human studies utilizing genome-wide association studies (GWAS), candidate gene analyses, whole exome sequencing (WES) and single-nucleotide polymorphisms (SNPs) in relation to MP. Additionally, insights from animal studies are incorporated to understand the molecular mechanisms underlying mandibular development and the pathogenesis of MP. A comprehensive literature search was conducted to identify relevant studies on the genetic basis of MP. Human studies employing GWAS, candidate gene analyses, and SNPs investigations were reviewed. Animal studies, including European seabass, zebrafish, transgenic mouse and miniature horse were also examined to provide additional insights into mandibular development and MP’s pathogenesis using GWAS, WES, transgenic techniques, morpholino antisense oligos and homozygote. Human studies have identified multiple loci and genes potentially associated with MP through GWAS, candidate gene analyses, and SNP investigations. Animal models have contributed valuable information about the molecular mechanisms involved in mandibular development and the development of MP. Recent research efforts have enhanced our understanding of the genetic etiology of MP. Integration of genetic studies with functional analyses has shed light on key signaling pathways and gene regulatory networks implicated in MP.

The temporomandibular joint (TMJ) is the critical functional unit in the human stomatognathic system. Damage of the TMJ causes orofacial dysfunction and secondary jaw deformities, leading to seriously decreased quality of life in patients. The TMJ prosthetic replacement is an important treatment method for severe joint destruction because of its remarkable advantages compared with other methods. In recent years, this technique has gradually attracted wide attention in China, but it has not been popularized on a large scale in our country because of several limitations. Thus, in this study, the clinical experience of patients with TMJ prosthetic replacement in clinical units was summarized, and the treatment principles, treatment processes, and technical advantages were systematically discussed, aiming to promote the popularization and application of TMJ prosthetic replacement in China.

Objetives To investigate the positional changes in the temporomandibular joint (TMJ) disc–condyle–fossa complex of patients with anterior disc displacement without reduction (ADDWoR) and to evaluate the effect of disc repositioning (DR) surgery. Material and methods Fifteen patients with unilateral ADDWoR (30 joints) were included. MRI of the TMJ was performed at T0 (1 week before surgery), T1 (1 month after surgery), and T2 (9–12 months after surgery). The glenoid fossa, disc, and condyle were reconstructed and analyzed using Mimics software. Results In the patients with unilateral ADDWoR, the disc on the ADD side showed a tendency to downward shift in the coronal direction and forward shift in the sagittal direction; the condyle of ADD side showed a tendency to backward shift in the sagittal direction and upward shift in the coronal direction. When comparing the same ADDwoR TMJ at T0, T1, and T2, the disc was found to move upward and backward after DR surgery at T1 and T2, and the condyle was found to move upward and backward after DR surgery at T1 but returned to the original position at T2. Conclusions ADDWoR leads to forward and downward displacement of the disc relative to the condyle and upward displacement of the condyle relative to the tuberosity. DR surgery improved upon the structural abnormalities of the TMJ complex, for which stability was maintained as determined in the 9 to 12 month postoperative follow-up. Clinic relevance DR surgery effectively and constantly improves the positional abnormalities of the TMJ complex.

OA is the most common joint disease that affects approximately 7% of the global population. Current treatment methods mainly relieve its symptoms with limited repairing effect on joint destructions, which ultimately contributes to the high morbidity rate of OA. Stem cell treatment is a potential regenerative medical therapy for joint repair in OA, but the uncertainty in differentiation direction and immunogenicity limits its clinical usage. Small extracellular vesicles (sEVs), the by-products secreted by stem cells, show similar efficacy levels but have safer regenerative repair effect without potential adverse outcomes, and have recently drawn attention from the broader research community. A series of research works and reviews have been performed in the last decade, providing references for the application of various exogenous therapeutic sEVs for treating OA. However, the clinical potential of target intervention involving endogenous pathogenic sEVs in the treatment of OA is still under-explored and under-discussed. In this review, and for the first time, we emphasize the dual role of sEVs in OA and explain the effects of sEVs on various joint tissues from both the pathogenic and therapeutic aspects. Our aim is to provide a reference for future research in the field.

The treatments generally employed for temporomandibular joint osteoarthritis (TMJOA) involve physical therapy and chemotherapy, etc., whose therapeutic efficacies are impaired by the side effects and suboptimal stimulus responsiveness. Although the intra-articular drug delivery system (DDS) has shown effectiveness in addressing osteoarthritis, there is currently little reported research regarding the use of stimuli-responsive DDS in managing TMJOA. Herein, we prepared a novel near-infrared (NIR) light-sensitive DDS (DS-TD/MPDA) by using mesoporous polydopamine nanospheres (MPDA) as NIR responders and drug carriers; diclofenac sodium (DS) as the anti-inflammatory medication; and 1-tetradecanol (TD) with a phase-inversion temperature of 39 °C as the drug administrator. Upon exposure to 808 nm NIR laser, DS-TD/MPDA could raise the temperature up to the melting point of TD through photothermal conversion, and intelligently trigger DS release. The resultant nanospheres exhibited an excellent photothermal effect and effectively controlled the release of DS through laser irradiation to accommodate the multifunctional therapeutic effect. More importantly, the biological evaluation of DS-TD/MPDA for TMJOA treatment was also performed for the first time. The experiments’ results demonstrated that DS-TD/MPDA displayed a good biocompatibility in vitro and in vivo during metabolism. After injection into the TMJ of rats afflicted with TMJOA induced by unilateral anterior crossbite for 14 days, DS-TD/MPDA could alleviate the deterioration of TMJ cartilage, thus ameliorating osteoarthritis. Therefore, DS-TD/MPDA could be a promising candidate for photothermal-chemotherapy for TMJOA.

Resulting from bacterial infection, apical periodontitis (AP) is a common inflammatory disease of the periapical region of the tooth. The regeneration of the destroyed periapical alveolar bone and the surrounding periodontium tissues has long been a difficult task in clinical practice. These lesions are closely related to pathogen invasion and an overreactive immune response. It is worth noting that the protective healing process occurs simultaneously, in which mesenchymal stem cells (MSCs) have a crucial function in mediating the immune system and promoting regeneration. Here, we review the recent studies related to AP, with a focus on the regulatory network of MSCs. We also discuss the potential therapeutic approaches of MSCs in inflammatory diseases to provide a basis for promoting tissue regeneration and modulating inflammation in AP. A deeper understanding of the protective action of MSCs and the regulatory networks will help to delineate the underlying mechanisms of AP and pave the way for stem-cell-based regenerative medicine in the future.