Overloading stress-induced condylar cartilage degeneration acts as the main pathologic change in temporomandibular joint osteoarthritis (TMJ-OA). However, the progression of degeneration and the ability for self-repair remain poorly understood. Here, we explored the progression of cartilage degeneration by dividing pathological stages using a steady mouth-opening mouse model. Then, we observed changes of cartilage by removing the loading at different stages to test the potential self-repair after degeneration induced. Three-dimensional confocal microscopy combined with histology and micro-CT scanning was applied to examine TMJ at different stages of degeneration before and after self-repair. We found the cartilage underwent progressive and thorough degeneration as the overloading stress developed. During the initial adaptation stage, robust proliferation of posteromedial cartilage began at the area of direct loading. Subsequently, widespread chondrocyte apoptosis was found, followed by new chondrocyte proliferation in aggregates with matrix degradation and subchondral bone catabolism. Finally, with cartilage surface damage, the degeneration reached a point where the lesion could not be reversed by self-repair. While the cartilage nearly returned to normal when the interference was removed within 5 days. These results suggested overloading force induces a pathological process of successive degeneration in TMJ cartilage, which can be reversed by self-repair at early stages.

Background Periodontitis and orthodontic treatment can lead to inflammatory root resorption (IRR) through an unclear mechanism. Chemerin, a novel chemoattractant protein, is closely associated with inflammation, affects osteoblast and osteoclast differentiation, and may play a role in IRR. We aimed to explore possible roles of the chemerin/ChemR23 interaction in cementoblast function and IRR and reveal a new IRR therapeutic target. Methods Cementoblast function‐related gene and protein expression in the immortalized murine cementoblast cell line OCCM‐30 after treatment with chemerin and siChemR23 was examined by qRT‐PCR and Western blotting. The roles of the MAPK and PI3K‐Akt signaling pathways were studied using specific inhibitors. Cementoblast cytokine production under different treatment conditions was measured by enzyme‐linked immunosorbent assay and qRT‐PCR. Additionally, we modeled IRR in wild‐type and chemerin‐overexpressing mice and injected transgenic mice with anti‐ChemR23 antibody to block ChemR23. We then calculated the root resorption volume and examined periodontal tissue cathepsin K, Runx2, tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) expression. Result Chemerin suppressed cementoblast differentiation and mineralization and exerted a proinflammatory effect on cementoblasts. These effects were partially reversed by siChemR23 and reversed to different extents by p38, Erk1/2 and PI3K‐Akt pathway inhibition, suggesting p38, Erk1/2 and PI3K‐Akt pathways as signaling pathways downstream of chemerin/ChemR23. In vivo, chemerin overexpression worsened IRR. Moreover, chemerin expression was positively correlated with TNF‐α, IL‐6, and cathepsin K expression and negatively correlated with Runx2 expression. ChemR23 downregulation reversed these effects. Conclusion Chemerin/ChemR23 induced TNF‐α and IL‐6 expression dependent on Erk1/2, p38 MAPK, and PI3K‐Akt signaling pathway activation, thereby regulating cementoblast function and affecting IRR.

Obesity has become increasingly prevalent. In the past 40 years, the prevalence of obesity has increased from less than 1% to 6%-8% in children, from 3% to 11% in men, and from 6% to 15% in women during the period of 1975(Jaacks et al., 2019. The rise in obesity poses a great threat to human health and has become a major healthcare challenge in all populations (

Background L‐arginine (L‐arg) can reduce apoptosis in a variety of cells. Cementoblast apoptosis is related to root resorption during orthodontic treatment. In the present study, we aimed to study the regulatory effect and potential mechanism of L‐arg on cementoblast apoptosis and root resorption. Methods The apoptosis‐related mRNA and protein expression of murine cementoblast (OCCM‐30) was assessed after L‐arg treatment. To investigate the role of Sirtuin 1 (Sirt1) and autophagy in L‐arg resistance to cementoblast apoptosis and root absorption, resveratrol, and EX527 were used to activate or inhibit Sirt1, and chloroquine (CQ) was used to inhibit autophagy. Results In vitro, L‐arg inhibited hypoxia‐induced apoptosis in OCCM‐30. Further, L‐arg increased Sirt1 expression whereas Sirt1 suppression by EX527 reversed the inhibitory effect of L‐arg on cell apoptosis. Sirt1 activator resveratrol increased the ratio of microtubule‑associated protein light chain 3 (LC3) II/I and decreased the expression of SQSTM1/p62 (p62), suggesting autophagy activation. Autophagy enhancement could reduce apoptosis. Caspase‐3 and Bax expression was decreased, and Bcl‐2 expression was increased. When autophagy was inhibited by CQ, the positive effects of Sirt1 were attenuated. In vivo, L‐arg application reduced root resorption in rats, as demonstrated by decreased root absorption volume. Similarly, L‐arg upregulated Sirt1, which activated autophagy in the root resorption model, and less root resorption was observed in the Sirt1 activation group. Conclusion L‐arg reduced cementoblast apoptosis in hypoxia and reduced root resorption induced by loading force in rats, which may be partly mediated by Sirt1‐enhanced autophagy.