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Objectives Interleukin (IL)‐37 is a natural suppressor of innate inflammation. This study was conducted to explore the anti‐inflammatory effects of IL‐37 in temporomandibular joint (TMJ) inflammation. Materials and Methods The expression of IL‐37 in the TMJ was measured using ELISA and IHC. Human TMJ chondrocytes were treated with IL‐37b and IL‐1β, and inflammation‐related factors were detected. siRNA‐IL‐1R8 was transfected into chondrocytes, and the affected pathways were detected. IL‐37b was used in disc‐perforation‐induced TMJ inflammation in SD rats. Micro‐CT, IHC, real‐time PCR and histological staining were used to quantify the therapeutic effect of IL‐37b. Results IL‐37 was expressed in the synovium and the disc of patients with osteoarthritis (OA) and in the articular cartilage of condylar fracture patients. IL‐37 was highly expressed in synovial fluid of patients with synovitis than in those with OA and disc displacement and was closely related to visual analogue scale (VAS) score. In vitro, IL‐37b suppressed the expression of pro‐inflammatory factors. In addition, IL‐37b exerted anti‐inflammatory effects via IL‐1R8 by inhibiting the p38, ERK, JNK and NF‐κB activation, while silencing IL‐1R8 led to inflammation and upregulation of these signals. In disc‐perforation‐induced TMJ inflammation in SD rats, IL‐37b suppressed inflammation and inhibited osteoclast formation to protect against TMJ. Conclusions IL‐37b may be a novel therapeutic agent for TMJ inflammation.

Teeth arise from the tooth germ through sequential and reciprocal interactions between immature epithelium and mesenchyme during development. However, the detailed mechanism underlying tooth development from tooth germ mesenchymal cells (TGMCs) remains to be fully understood. Here, we investigate the role of Wnt/β‐catenin signalling in BMP9‐induced osteogenic/odontogenic differentiation of TGMCs. We first established the reversibly immortalized TGMCs (iTGMCs) derived from young mouse mandibular molar tooth germs using a retroviral vector expressing SV40 T antigen flanked with the FRT sites. We demonstrated that BMP9 effectively induced expression of osteogenic markers alkaline phosphatase, collagen A1 and osteocalcin in iTGMCs, as well as in vitro matrix mineralization, which could be remarkably blunted by knocking down β‐catenin expression. In vivo implantation assay revealed that while BMP9‐stimulated iTGMCs induced robust formation of ectopic bone, knocking down β‐catenin expression in iTGMCs remarkably diminished BMP9‐initiated osteogenic/odontogenic differentiation potential of these cells. Taken together, these discoveries strongly demonstrate that reversibly immortalized iTGMCs retained osteogenic/odontogenic ability upon BMP9 stimulation, but this process required the participation of canonical Wnt signalling both in vitro and in vivo. Therefore, BMP9 has a potential to be applied as an efficacious bio‐factor in osteo/odontogenic regeneration and tooth engineering. Furthermore, the iTGMCs may serve as an important resource for translational studies in tooth tissue engineering.

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