Next, immunohistochemical staining, ELISA, and immunofluorescence staining revealed that the expression of β-catenin and C-myc in the synovium (Figure 5C), the serum levels of IL-6 and IL-8 (Figure 5D), as well as expression of MMP3 (Figure 5E) in the synovial membrane of rats, all were markedly increased by upregulation of HOTTIP or silencing of SFRP1 in RA rats but decreased when HOTTIP was silenced or SFRP1 was overexpressed. The gene discussed is HOTTIP; the disease is rheumatoid arthritis.