Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand

The RANK/RANKL/osteoprotegerin system in rheumatoid arthritis: New insights from animal models

“…Besides its role in bone resorption and osteoclastogenesis, RANKL has immunologic properties and is expressed in activated T cells, lymph nodes, spleen, thymus, intestinal lymphoid patches, and immature CD4/CD8 thymocytes (9,10,18). RANK is expressed on the surface of DCs, mature T cells and hematopoietic precursors.…”

“…RANKL is expressed by lymphocytes, macrophages, and, in RA, also by synovial fibroblasts (57). RA synovial fibroblasts therefore appear to be additional sources for RANKL (18). In this regard, it has been shown that the induction of TRAP-positive multinucleated osteoclasts derived from peripheral blood mononuclear cells depends on the level of RANKL produced by cultured RA synovial fibroblasts (57).…”

“…Inhibition of RANKL via OPG at the time of disease onset can prevent bone erosion (18). In addition, in a model of TNF␣-induced arthritis, OPG treatment is beneficial in terms of cartilage destruction, without affecting inflammation (60,61).…”

“…RANKL expressed on activated T cells can trigger osteoclast activation, and therefore, RANK/RANKL might have a role in inflammation-induced bone loss and joint destruction in RA (18). Similarly, in type II collagen-induced arthritis in mice, RANK/RANKL plays an important role in osteoclastogenesis in local and systemic osteolytic lesions (64).…”

“…Most important, it is also expressed by activated T lymphocytes and immature CD4/CD8 thymocytes (17). Moreover, the presence of RANKL in organs such as lymph nodes, spleen, thymus, and intestinal lymphoid patches has been described (9,10,18). RANKL is increased upon exposure to factors that promote osteoclast development, such as vitamin D 3 and prostaglandin E 2 (PGE 2 ), which also diminish the expression of OPG by osteoblasts (19).…”