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. 2014 Jan 11;11(3):240-5.
doi: 10.7150/ijms.7489. eCollection 2014.

Stromal cell-derived factor-1 and its receptor CXCR4 are upregulated expression in degenerated intervertebral discs

Hua Zhang  1 , Li Zhang  2 , Linwei Chen  1 , Wanli Li  1 , Fangcai Li  1 , Qixin Chen  1
Affiliations

Stromal cell-derived factor-1 and its receptor CXCR4 are upregulated expression in degenerated intervertebral discs

Hua Zhang et al. Int J Med Sci. .

Abstract

Background: Although chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 induce degradation of articular cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA), the association between the SDF-1/CXCR4 pathway and degradation of the cartilaginous endplate and nucleus pulposus has not been thoroughly clarified. We investigated the expression of SDF-1 and CXCR4 in intervertebral discs (IVDs).

Methods: SDF-1 and CXCR4 levels in human IVDs and the rat L5/6 motion segment were quantified by enzyme-linked immunosorbent assay. SDF-1 staining was quantified using a microscope and Image-Pro Plus software. Integrated optical density (IOD) served as the measurement parameter. The number of CXCR4 immunoreactive cells was expressed as a percentage of the total number of cells.

Results: SDF-1 and CXCR4 were both expressed in IVDs, and the levels of SDF-1 and CXCR4 were both significantly higher in the degeneration group than in the normal group of human (or rat) discs. Both nucleus pulposus cells and cartilaginous endplate cells expressed the CXCR4 protein. Furthermore, a positive correlation was observed between the SDF-1 IOD value and the percentage of CXCR4-positive disc cells in the nucleus pulposus and cartilaginous endplate. The SDF-1 IOD values were significantly higher in the outer annular fibrosus and bone/endplate junction region than in the nucleus pulposus and cartilaginous endplate in the rat specimens.

Conclusions: Our findings suggest upregulated expression of SDF-1 and its receptor CXCR4 in degenerated IVD.

Keywords: CXCR4; SDF-1; endplate; intervertebral disc; nucleus pulposus.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Under a light microscope, both CXCR4 (A-D) and SDF-1 (E-H) appear light brown by in situ immunohistochemical staining of human intervertebral disc specimens. CXCR4 was expressed by the nucleus pulposus and endplate cartilage cells, while SDF-1 was found mainly in the extracellular matrix. Patients with lumbar disc herniation (Pfirrmann grade V) had high CXCR4 expression in the (A) cartilage endplate (×40) and (B) nucleus pulposus (×40), and high SDF-1 expression in the (E) cartilage endplate (×20) and (F) nucleus pulposus (×40). Patients with lumbar fractures (Pfirrmann grade I) had low CXCR4 expression in the (C) cartilage endplate (×40) and (D) nucleus pulposus (×40) and low SDF-1 expression in the (G) cartilage endplate (×20) and (H) nucleus pulposus (×20)
Figure 2
Figure 2
Under a light microscope, SDF-1 (A-F) and CXCR4 (G-J) both appear light brown by in situ immunohistochemical staining of rat vertebral-intervertebral disc-vertebral segment specimens. (A) The thick arrow indicates the nucleus; the thin arrow indicates the cartilage end plate (×5). (B) The nucleus pulposus expressed SDF-1 mainly in the extracellular matrix (×20). (C) SDF-1 expression was lower in cartilage endplate cells and the surrounding area and high in the capillary sinus (×40). (D) The vertebral body near the endplate was rich in SDF-1, suggesting that the bone marrow stromal cells in this area were the main source of SDF-1 for the disc (×20). (E) The thick arrow indicates the outer annular fibrosus; the thin arrow indicates the inner annular fibrosus (×5). (F) The outer annular fibrosus tissue showed strong positive staining, indicating that fibroblasts expressed SDF-1 (×40). (G) The distribution of CXCR4 expression in the vertebral body-intervertebral disc-vertebral segment (×5). (H-J) CXCR4 expression by nucleus pulposus cells, endplate chondrocytes, and osteoblasts, respectively.
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