Furthermore, hyperplastic synovial tissue can be considered to provide a suitable microenvironment for osteoclastogenesis, since synovial fibroblasts and immune cells serve as potential nursing cells (Gravallese et al., 2000; Takayanagi et al., 1997), and express RANKL to induce differentiation of osteoclast directly involved in lesions of RA (Yang et al., 2014). This evidence concerns the gene TNFSF11 and rheumatoid arthritis.