The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Objective: To analyze the correlation between third molar agenesis and craniofacial morphology by studying the location and number of congenital missing third molars and results of craniofacial cephalometric measurement. Methods: A total of 123 patients were included, including 64 patients in the control group without congenital third molar absence and 59 patients in the absence group with at least one third molar absent. Cephalometric measurements included FMA, IMPA, AR-Go, GoGn-Sn, Co-A, Co-Gn, ANS-Me, Go-Me, SN-MP, Ar-Go-Me, SNA, SNB, ANB, Y-axis angle, Y-axis length, Ar-Go, Go-Me, MP-OP, FH-PP, FH-OP, a total of 18 bone tissue indicators, U1-SN, U1-L1, U1-NA, L1-NB, U1-APo and L1-APo, a total of 6 dental indicators, and UL-EP, LL-EP and nasolabial angle, a total of 3 soft tissue indicators. The correlation between congenital agenesis of third molars and craniofacial morphology was analyzed. Results: The most common missing location of the third molar occured in the upper jaw and the most common number of missing teeth was one. In control group, Ar-Go-Me and SN-MP were larger (P<0.05), U1-SN, U1-NA, L1-NB, UL-EP and LL-EP were larger (P<0.05), and U1-L1 was smaller (P<0.01). There were no significant differences in Ar-Go and Go-Me between the two groups(P>0.05). Conclusion Patients with four third molars are more likely to have backward and downward rotation of the mandible and are more likely to develop into a convex facial type than patients with missing third molars, which has a higher correlation with hyperdivergent growth pattern and convex facial type.

Objective: To investigate craniofacial differences in individuals with hypodontia and explore the relationship between craniofacial features and the number of congenitally missing teeth. Methods: A cross-sectional study was conducted among 261 Chinese patients (males, 124; females, 137; age, 7–24 years), divided into four groups (without hypodontia: no teeth missing, mild: one or two missing teeth, moderate: three to five missing teeth, severe: six or more missing teeth) according to the number of congenitally missing teeth. Differences in cephalometric measurements among the groups were analyzed. Further, multivariate linear regression and smooth curve fitting were performed to evaluate the relationship between the number of congenitally missing teeth and the cephalometric measurements. Results: In patients with hypodontia, SNA, NA-AP, FH-NA, ANB, Wits, ANS-Me/N-Me, GoGn-SN, UL-EP, and LL-EP significantly decreased, while Pog-NB, AB-NP, N-ANS, and S-Go/N-Me significantly increased. In multivariate linear regression analysis, SNB, Pog-NB, and S-Go/N-Me were positively related to the number of congenitally missing teeth. In contrast, NA-AP, FH-NA, ANB, Wits, N-Me, ANS-Me, ANS-Me/N-Me, GoGn-SN, SGn-FH (Y-axis), UL-EP, and LL-EP were negatively related, with absolute values of regression coefficients ranging from 0.147 to 0.357. Further, NA-AP, Pog-NB, S-Go/N-Me, and GoGn-SN showed the same tendency in both sexes, whereas UL-EP and LL-EP were different. Conclusions Compared with controls, patients with hypodontia tend toward a Class III skeletal relationship, reduced lower anterior face height, flatter mandibular plane, and more retrusive lips. The number of congenitally missing teeth had a greater effect on certain characteristics of craniofacial morphology in males than in females.

Skeletal angle class Ⅲ malocclusion with mandibular deviation involves the rotation and translation of the cranial base, maxilla, mandible, and soft tissue. It compromises the patients’ appearance and stomatognathic function. The treatment outcome is not satisfactory, and correct evaluation is of great significance. The causal relationship between skeletal Class Ⅲ with mandibular deviation and TMD remains controversial. This review focuses on the structural alterations of hard and soft tissue, the etiology, the choice of treatment methods, and the association with TMD in patients with skeletal class Ⅲ malocclusion with mandibular deviation. The results show that mandibular deviation is a complex disease with unclear etiology. It involves morphological changes, rotation and displacement of the cranial base, maxilla and mandible, morphological changes of the soft tissue, and occlusal changes, which also compromise the temporomandibular joint and mandibular function. Skeletal Class Ⅲ malocclusion is common in patients with mandibular deviation. Early treatment is needed; however, the treatment methods vary. The correct evaluation of the morphological changes of soft and hard tissues leading to facial asymmetry is the premise of treatment. Orthodontic and orthognathic treatment (combined with soft tissue repair when necessary) is an effective method for the treatment of skeletal class Ⅲ malocclusion with mandibular deviation. In addition, there is a close relationship between mandibular deviation and TMD, which needs to be fully considered in the design of treatment.