Thirdly, they are involved in the bone metabolism, since OPN is a key bone component produced by osteoblasts, whereas ICOS-mediated triggering of ICOSL expressed by osteoclasts (OC) inhibits OC differentiation from monocytes and bone resorption activity of mature OC in vitro, and the development of osteoporosis in vivo18. This evidence concerns the gene BGLAP and osteoporosis.