TNF and rheumatoid arthritis: This pathway is crucial to many aspects of cell growth and survival in both physiological as well as in pathological conditions.[40] It has been demonstrated that the PI3K-Akt signaling pathway can be activated by several cytokines such as TNF-α in RA synoviocytes.[41] Moreover, module analysis of the PPI network of OA suggested that the development and progression of OA were related to the Wnt signaling pathway.