The immune and skeletal systems share various molecules, including cytokines, transcription factors, signaling molecules and membrane receptors(1).
RANKL is a key cytokine for osteoclast differentation expressed by msenchymal cells including osteoblastic cells as well as hematopoietic cells like T cell, thus it has been difficult to precisely characterize RANKL-expressing cells under physiological and pathological settings (2). The source of RANKL in bone has been thought to be osteoblasts or bone marrow stromal cells, but osteocyte-specific RANKL knockout mice revealed the crucial role of osteocytes in supporting osteoclastogenesis in adult bone remodeling (3). In autoimmune arthritis, RANKL is expressed by joint mesenchymal cells like synovial fibroblasts stimulated with IL-17 and other inflammatory cytokines. RANKL signal transduction is mediated by numerous immune-related molecules including NFATc1 and ITAM, which shed light on the mechanisms shared by the bone and the immune systems (2).
Here I will review the history of osteoimmunology and discuss the emerging topics in osteoimmunology including bone cell communication factors in the regulation of bone formation by osteoclast-derived Sema4D (4) and osteoprotection by osteoblast-derived Sema3A (5).
Nat Rev Immunol 7, 292-304, 2007
Nat Rev Rheumatol 5, 667-76, 2009
Nat Med 17, 1231-34, 2011
Nat Med. 17, 1473-80, 2011
Nature 485, 69-74, 2012
Disclosure of Interest None Declared