Upregulation of β-catenin signaling represents a single common pathway leading to the various phenotypes of spinal degeneration and pain

Spine degeneration is an aging-related disease, but its molecular mechanisms remain unknown, although elevated beta-catenin signaling has been reported to be involved in intervertebral disc degeneration. Here, we determined the role of beta-catenin signaling in spinal degeneration and in the homeostasis of the functional spinal unit (FSU), which includes the intervertebral disc, vertebra and facet joint and is the smallest physiological motion unit of the spine. We showed that pain sensitivity in patients with spinal degeneration is highly correlated with beta-catenin protein levels. We then generated a mouse model of spinal degeneration by transgenic expression of constitutively active beta-catenin in Col2(+) cells. We found that beta-catenin-TCF7 activated the transcription of CCL2, a known critical factor in osteoarthritic pain. Using a lumbar spine instability model, we showed that a beta-catenin inhibitor relieved low back pain. Our study indicates that beta-catenin plays a critical role in maintaining spine tissue homeostasis, its abnormal upregulation leads to severe spinal degeneration, and its targeting could be an avenue to treat this condition.

Automated summary

This study reveals the crucial role of beta-catenin signaling in spinal degeneration and its correlation with pain sensitivity in patients. The inhibition of beta-catenin can alleviate low back pain, suggesting its potential as a therapeutic target for spinal degeneration.