The Role of Toll-Like Receptors in Osteoclastogenesis

ABSTRACT

Bone homeostasis is maintained by a balance in the levels of osteoclast and osteoblast activity. Osteoclasts are bone-resorbing cells and have been shown to act as key players in various osteolytic diseases. Osteoclasts differentiate from monocyte/macrophage lineage cells in the presence of receptor activator of nuclear factor-κB ligand and macrophage colony-stimulating factor. Osteoblasts support osteoclastogenesis by producing several osteoclast differentiation factors. Toll-like receptors (TLRs) are members of the pattern recognition receptor family that are involved in recognizing pathogen-associated molecular patterns and damage-associated molecular patterns in response to pathogen infection. TLRs regulate osteoclastogenesis and bone resorption through either the myeloid differentiation primary response 88 or the Toll/interleukin-1 receptor domaincontaining adapter-inducing interferon-β signaling pathways. Since osteoclasts play a central role in the progression of osteolytic diseases, extensive research focusing on TLR downstream signaling in these cells should be conducted to advance the development of effective TLR modulators. In this review, we summarize the currently available information on the role of TLRs in osteoclast differentiation and osteolytic diseases.