Monomeric CRP regulates inflammatory responses in human intervertebral disc cells

Area of Science:

• Biochemistry and Molecular Biology
• Cell Biology
• Biomaterials Science

Background:

• C-reactive protein (CRP) is an acute-phase protein with poorly defined pathophysiological roles.
• Pentameric CRP has weak anti-inflammatory effects, while monomeric CRP (mCRP) is proinflammatory in various cell types.
• No data existed on mCRP's effects in human intervertebral disc (IVD) cells, despite its potential relevance to IVD degeneration.

Purpose of the Study:

• To investigate the pathophysiological relevance of mCRP in the etiology and progression of human IVD degeneration.
• To examine the effects of mCRP on human annulus fibrosus (AF) and nucleus pulposus (NP) cells.
• To identify the intracellular signaling pathways involved in mCRP's effects on IVD cells.

Main Methods:

• Cultured human primary AF cells and immortalized HNPSV-1 NP cells were treated with mCRP.
• Quantitative real-time PCR (RT-qPCR) and Western blot were used to measure mRNA and protein levels of inflammatory factors.
• Immunohistochemistry was employed to detect mCRP presence in human AF and NP tissues.

Main Results:

• mCRP significantly increased the expression of NOS2, COX2, MMP13, VCAM1, IL-6, IL-8, and LCN2 in human AF and NP cells.
• Intracellular signaling pathways involving NF-κβ, ERK1/2, and PI3K were identified as mediators of mCRP's effects.
• mCRP was detected in human AF and NP tissues, indicating its presence in the IVD microenvironment.

Conclusions:

• This study demonstrates for the first time the presence and proinflammatory role of mCRP in human IVD tissues.
• mCRP induces a proinflammatory and catabolic state in both healthy and degenerated human IVD cells.
• NF-κβ signaling is implicated in mediating the effects of mCRP in the intervertebral disc.