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The TNF receptor superfamily

Role in immune inflammation and bone formation

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Abstract

Tumor necrosis factor (TNF) and TNF receptor (TNFR) family proteins play important roles in many biological processes. Recently, the TNF-family molecule, RANKL (also called TRANCE, ODF, and OPGL), and its receptors, RANK and OPG, were found to be regulators of the development and activation of osteoclasts in bone remodeling. TNFα also activates osteoclasts both by themselves and in synergy with RANKL. We used structure-based design to create peptidomimetics and organic therapeutics that inhibit osteoclastogenesis by inhibiting the interaction of ligands and receptors. Here we show for the first time that blocking TNFα by these small molecules effectively inhibited osteoclast formation in vitro. These mimetics can be used as a probe to understand the molecular basis of osteoclastogenesis and also as a platform to create useful therapeutic agent.

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Authors and Affiliations

  1. Department of Pathology and Laboratory of Medicine, Abramson Institute for Cancer Research, University of Pennsylvania, 252 John Morgan Bldg., 19104-6082, Philadelphia, PA

    Xin Cheng, Masa Kinosaki, Ramachandran Murali & Mark I. Greene

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  1. Xin Cheng
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  2. Masa Kinosaki
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  3. Ramachandran Murali
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  4. Mark I. Greene
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Correspondence to Ramachandran Murali or Mark I. Greene.

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Cheng, X., Kinosaki, M., Murali, R. et al. The TNF receptor superfamily. Immunol Res 27, 287–294 (2003). https://doi.org/10.1385/IR:27:2-3:287

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