The role of IL-31 in bone remodeling. IL-31, mainly produced by T helper 2 memory cells (Th2 CD45RO+), promotes osteoclastogenesis by inducing the differentiation of osteoclast progenitors (OCP) into mature osteoclasts (OC). IL-31, in synergy with reactive oxygen species (ROS), also stimulates osteoclastogenesis indirectly by inducing antigen-presenting cells (APC), monocytes, and T helper 1 and 17 lymphocytes (Th1/Th17) to produce chemokines, metalloproteinases, and inflammatory cytokines, which in turn increase the production of IL-31. All of these events lead to the development of osteoporosis.