PURPOSE OF REVIEW: The mechanisms involved in the TNF-mediated deregulated bone remodeling are little appreciated. This review will discuss and summarize the impact of TNF, Notch, and RBP-J signaling on bone remodeling. RECENT FINDINGS: The integrity of the adult skeleton undergoes constant and dynamic remodeling throughout life to maintain a proper bone homeostasis, which is achieved by the essential tight control of coupling between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. The studies in this field include not only the differentiation and function of osteoblasts and osteoclasts, but also the mechanisms that simultaneously control both cell types during bone remodeling. Chronic inflammation is one of the most evident and common pathological settings that often leads to deregulated bone remodeling. The resounding success of TNF blockade therapy has demonstrated a key role for TNF in inflammation and the pathogenesis of inflammatory bone resorption associated with diseases such as rheumatoid arthritis and periodontitis. Recent studies have highlighted the function of Notch and RBP-J signaling in both physiological and TNF-mediated inflammatory bone remodeling.
