HISTOLOGY AND HISTOPATHOLOGY

From Cell Biology to Tissue Engineering

 

Review

TWEAK/Fn14 signaling: a promising target in intervertebral disc degeneration

Yu-Ping Liu1, Chong-Ming Yuan1, Shuai-Gong Zhang1, Qing-Hai Hao1, Ming-Ming Wang1, Zhong Zhang1, Qian Meng1, Ming Li1 and Yue-Dong Hao2

1Department of Orthopedics, Tengzhou Central People's Hospital, Tengzhou Shandong and 2Department of Orthopedics, Huaian First People's Hospital, Huaian Jiangsu, P.R. China

Offprint requests to: Yue-Dong Hao, Department of Orthopedics, Huaian First People's Hospital, Huaian Jiangsu, P.R. China. e-mail: hyd1975@139.com


Summary. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a potent chemo-attractant cytokine with various biological functions, such as stimulation of angiogenesis, induction of proinflammatory cytokines, regulation of cellular proliferation and apoptosis. Therefore, it has also been implicated in several pathological processes, from cancer to inflammatory diseases. Remarkably, TWEAK and its receptors, fibroblast growth factor inducible 14 (Fn14), are also present in intervertebral disc (IVD) tissue, where they play a role in the pathogenesis of IVD degeneration. The interaction of TWEAK with Fn14 is involved in physiological and pathological activities of IVD degeneration patients, which includes apoptosis of endplate chondrocytes, extracellular matrix degradation, reduction in proteoglycan synthesis and so on. The blockade of this interaction results in suppressing over-production of proinflammatory factors and cell death in in vivo or in vitro experiments, suggesting that TWEAK/Fn14 signaling may be therapeutically relevant in IVD degeneration, and the targeting of TWEAK or Fn14 has been proposed as a potential therapeutic approach for autoimmune diseases such as Rheumatoid arthritis (RA). In this article, we discuss the biological features of TWEAK/Fn14 signaling and summarize recent advances in our understanding of the role of TWEAK/Fn14 signaling in the pathogenesis and treatment of IVD degeneration. We think that the blockade of TWEAK/Fn14 signaling may be a promising therapeutic strategy for IVD degeneration in the near future. Histol Histopathol 31, 943-948 (2016)

Key words: TWEAK, Fn14, Target, Intervertebral disc, Degeneration

DOI: 10.14670/HH-11-775