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)‑1β‑stimulated temporomandibular chondrocytes remain to be elucidated. In the present study, chondrocytes were isolated from Sprague‑Dawley rats and stimulated by IL‑1β 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‑κB (NF‑κB) was also analyzed. Compared with the control, IL‑1β stimulation increased the expression of Notch1 and NICD. In addition, IL‑1β stimulation increased the secretion of tumor necrosis factor‑α 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‑κB 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‑1β‑induced inflammatory response partly by inhibiting the NF‑кB 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.