Abstract
Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine expressed by macrophages, monocytes, and T cells, and its expression is triggered by the immune system in response to pathogens and their products, such as endotoxins. TNF-α plays an important role in host defense by inducing inflammatory reactions such as phagocytes and cytocidal systems activation. TNF-α also plays an important role in bone metabolism and is associated with inflammatory bone diseases. TNF-α binds to two cell surface receptors, the 55kDa TNF receptor-1 (TNFR1) and the 75kDa TNF receptor-2 (TNFR2). Bone is in a constant state of turnover; it is continuously degraded and built via the process of bone remodeling, which results from the regulated balance between bone-resorbing osteoclasts, bone-forming osteoblasts, and the mechanosensory cell type osteocytes. Precise interactions between these cells maintain skeletal homeostasis. Studies have shown that TNF-α affects bone-related cells via TNFRs. Signaling through either receptor results in different outcomes in different cell types as well as in the same cell type. This review summarizes and discusses current research on the TNF-α and TNFR interaction and its role in bone-related cells.
Highlights
Skeletal health, architecture, and homeostasis are functions of the constant process of bone remodeling [1]
The formed osteoclasts were not functional, osteoclast functionality was recovered by TRAF6 activation via IL1 [65]. These findings suggest that Tumor necrosis factor-α (TNF-α)-induced osteoclast formation acts independent of RANK/RANKL, given that additional cofactors are supplemented and that TRAF6 is essential for osteoclast activation and function
Our studies found that TNF-α plays an essential role in orthodontic tooth movement (OTM) in both TNF receptor-1 (TNFR1)- and TNF receptor-2 (TNFR2)-deficient mice, which experienced less tooth movement distance compared to wild-type mice [81,82,83,84,85,86]
Summary
Architecture, and homeostasis are functions of the constant process of bone remodeling [1]. We showed that chimeras made of TNFRs deficient mice and wild-type mice can be used to examine the type of cell targeted by TNF-α for osteoclast formation during OTM. These findings suggested that the response of stromal cells to TNF-α is a crucial factor for osteoclast formation and bone resorption in OTM [83]. Analysis of bone marrow cells derived from mice differentially expressing TNFR1 or TNFR2 revealed that TNFR1 induced osteoclast formation results are comparable to those obtained in wild-type mice, and marrow from mice expressing only TNFR2 could not stimulate osteoclast formation [87]. These results suggested that selective signaling through TNFR1 or TNFR2 has different outcomes and that TNFR1 plays an essential role in TNF-α-induced osteoclast formation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
