The immune system, bone and RANKL

DHEA prevents bone loss by suppressing the expansion of CD4⁺ T cells and TNFa production in the OVX-mouse model for postmenopausal osteoporosis

“…RANKL is an osteoclastogenic mediator that is mainly expressed in bone by cells of mesenchymal origin (37). However, T cells can also be an important source of RANKL under certain conditions, such as PMO (37).…”

“…However, T cells can also be an important source of RANKL under certain conditions, such as PMO (37). CD4 + T cells have the potential to both positively and negatively impact osteoclastogenesis by secreting pro-osteoclastogenic cytokines like RANKL and by secreting cytokines to induce antiosteoclastogenic cytokine OPG expression (45,46).…”

“…Researchers have begun to recognize the fact that the skeletal and immune systems mutually regulate one another to a much greater degree than previously believed, and "osteoimmunology", an interdisciplinary research principle, plays many roles in the cross-talk between the bone and immune systems (37). PMO is known to be associated with a variety of endocrine and immune alterations (38).…”

Underlying Mechanisms and Therapeutic Strategies for Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ)

“…RANKL is expressed not only on osteoblasts, but also on activated T cells, dendritic cells, monocytes, macrophages, and keratinocytes. 91,92) Recent studies suggest that T cellderived RANKL may initiate immune system responses via activation of osteoclasts or bone loss. 91,92) Although IL-1 is considered to be the strongest cytokine for the activation of osteoclasts, we have suggested that the prime role of bone IL-1 in mice may lie in the emergency Ca 2+ -supply to soft tissues, not in bone-remodeling.…”

“…90) Receptor activator of nuclear factor-κB (RANK) and its ligand RANKL are key molecules not only in bone physiology, but also in immunity, pregnancy, and even in the central nervous system. 91,92) Indeed, RANKL and RANK play central roles in both osteoclastogenesis and lymph node organogenesis. RANKL is expressed not only on osteoblasts, but also on activated T cells, dendritic cells, monocytes, macrophages, and keratinocytes.…”