Related Experiment Video
Updated: Jul 14, 2026
06:03
Operational and Intervention Effects of Targeted Tuina in Lumbar Intervertebral Disc Degeneration Model Rabbits
Published on: July 21, 2023
Novel function of TWEAK in inducing intervertebral disc degeneration
Masanori Wako1, Hirotaka Haro, Takashi Ando
1Department of Orthopaedic Surgery, Graduate School of Medicine and Engineering, University of Yamanashi.
Summary
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 are present in intervertebral discs. TWEAK promotes disc degeneration by up-regulating MMP-3 and down-regulating aggrecan.
Area of Science:
- Biochemistry
- Cell Biology
- Orthopedics
Background:
- Intervertebral disc degeneration is a major cause of low back pain.
- The molecular mechanisms underlying disc degeneration are not fully understood.
- The cytokine TWEAK and its receptor Fn14 are implicated in various inflammatory and degenerative processes.
Purpose of the Study:
- To investigate the expression and role of TWEAK and Fn14 in normal and degenerating intervertebral disc tissues.
- To determine the effect of TWEAK on matrix metalloproteinase-3 (MMP-3) and aggrecan expression in disc cells.
- To elucidate the potential contribution of TWEAK to the pathogenesis of disc degeneration.
Main Methods:
- Histological examination of murine disc tissues.
- Murine organ disc culture to assess TWEAK's function.
- Immunohistochemistry and quantitative real-time PCR to confirm TWEAK and Fn14 expression.
- Treatment with recombinant TWEAK, neutralizing antibodies, and Fn14/Fc fusion proteins.
- Analysis of MMP-3 and aggrecan expression in response to TWEAK.
Main Results:
- TWEAK and Fn14 expression was confirmed in murine intervertebral discs.
- TWEAK dose- and time-dependently induced MMP-3 production in disc cells.
- TWEAK-induced MMP-3 up-regulation was inhibited by anti-TWEAK antibodies or Fn14/Fc fusion proteins.
- TWEAK significantly abrogated aggrecan expression in a time-dependent manner.
- TWEAK deficiency prevented MMP-3 expression, indicating its critical role.
Conclusions:
- TWEAK and its receptor Fn14 are expressed in murine intervertebral discs.
- TWEAK plays a significant role in promoting disc degeneration by up-regulating MMP-3 and down-regulating aggrecan.
- Targeting the TWEAK/Fn14 pathway may offer a therapeutic strategy for disc degeneration.
Related Concept Videos
01:27Degenerative Disc Disease I: Introduction
Degenerative disc disease is a chronic condition in which intervertebral discs gradually lose structure and function. It is not infectious or autoimmune; rather, it results from age-related biochemical and mechanical changes, influenced by genetic, metabolic, and environmental factors.Structure and Function of DiscsThe spine contains 23 intervertebral discs that absorb load, distribute forces, maintain spacing, and allow flexibility. Each disc consists of a nucleus pulposus, a gel-like core...
01:23Degenerative Disc Disease ll: Pathophysiology
The symptoms of degenerative disc disease arise from a combination of mechanical compression, vascular compromise, and biochemical inflammation, which together disrupt nerve function and produce pain.Mechanical CompressionDisc degeneration reduces height and elasticity, predisposing to herniation of the nucleus pulposus, a major cause of radicular pain. Herniations may be protrusion (bulging with intact annulus), extrusion (nucleus extends beyond disc but remains connected), or sequestration...
01:29Herniated Intervertebral Disc l: Introduction
Intervertebral disc herniation refers to the displacement of the nucleus pulposus (the gel-like inner core of the disc) through a tear or weakened area in the annulus fibrosus (the outer fibrous ring). The displaced disc material extends beyond the normal boundaries of the disc space and may compress or irritate nearby spinal nerve roots or, less commonly, the spinal cord.Etiology and Risk FactorsHerniation commonly results from degeneration, in which aging reduces disc hydration and...