Inhibition of Notch1 protects against IL-1β-induced inflammation and cartilage destruction in temporomandibular chondrocytes

Temporomandibular disorder (TMD) is a complex and multifactorial disease, with inflammatory response and cartilage destruction usually associated with its etiology. Notch1 is a type I transmembrane receptor, which is critical in determining the growth, differentiation and survival of various cell types. However, its role and mechanism in interleukin (IL)-1 beta-stimulated temporomandibular chondrocytes remain to be elucidated. In the present study, chondrocytes were isolated from Sprague-Dawley rats and stimulated by IL-1 beta at a concentration of 10 ng/ml, and the expression of Notch1 was inhibited by small interfering RNA. The expression levels of Notch1 and Notch1 intracellular domain (NICD) were analyzed using reverse transcription-quantitative polymerase chain reaction and western blot analyses. Matrix metalloproteinases (MMPs) and the tissue inhibitor of metalloproteinases (TIMPs) were assessed using western blot analysis, and nuclear factor-kappa B (NF-kappa B) was also analyzed. Compared with the control, IL-1 beta stimulation increased the expression of Notch1 and NICD. In addition, IL-1 beta stimulation increased the secretion of tumor necrosis factor-a and IL-6, and the expression of intercellular adhesion molecule 1 and inducible nitric oxide synthase. By contrast, inhibition of Notch1 reduced these inflammatory responses by suppressing the nuclear translocation and phosphorylation of NF-kappa B p65. The inhibition of Notch1 also reduced the expression of MMPs and increased the expression of TIMP-1. These data suggested that the inhibition of Notch1 prevented the IL-1 beta-induced inflammatory response partly by inhibiting the NF-kappa B signaling pathway in temporomandibular chondrocytes. The inhibition of Notch1 suppressed cartilage destruction by modulating the balance between MMPs and TIMP-1, therefore, inhibition of Notch1 may be a mechanism for the treatment of TMD.