Stromal cell‑derived factor‑1 induces matrix metalloproteinase expression in human endplate chondrocytes, cartilage endplate degradation in explant culture, and the amelioration of nucleus pulposus degeneration in vivo

Zhang,Hua; Zhu,Ting; Zhang,Li; Wu,Qionghua

doi:10.3892/ijmm.2017.3278

Stromal cell‑derived factor‑1 induces matrix metalloproteinase expression in human endplate chondrocytes, cartilage endplate degradation in explant culture, and the amelioration of nucleus pulposus degeneration in vivo

Authors:
- Hua Zhang
- Ting Zhu
- Li Zhang
- Qionghua Wu
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Affiliations: Department of Orthopaedic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Department of Clinical Laboratory, Hangzhou Red Cross Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310000, P.R. China
Published online on: November 22, 2017 https://doi.org/10.3892/ijmm.2017.3278
Pages: 969-976

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Abstract

Intervertebral disc (IVD) degeneration is a strong etiological factor in chronic lower back pain. Stem cell migration toward the site of IVD degeneration for regeneration is restricted by avascularity and distance. Our previous study indicated that the expression of stromal cell‑derived factor‑1 (SDF‑1) and its receptor, C-X-C chemokine receptor type 4 (CXCR4) was upregulated in degenerated cartilage endplate (CEP) and nucleus pulposus (NP). In the present study, SDF‑1 increased CXCR4 mRNA and protein expression in human endplate chondrocytes in a dose‑dependent manner. The results of reverse transcription-quantitative polymerase chain reaction, western blotting and zymography indicated that SDF‑1 increased matrix metalloproteinase (MMP)‑1, ‑3 and ‑13 mRNA and protein expression in human endplate chondrocytes in a dose‑dependent manner. The results of zymography suggested that SDF‑1 also increased MMP‑2 and ‑9 protein expression in a dose‑dependent manner. The CXCR4‑specific chemical inhibitor AMD3100 significantly decreased the levels of MMP‑1, ‑2, ‑3, ‑9 and ‑13 expression. In a human cartilage explant culture model, SDF‑1 accelerated the degradation of extracellular matrix (ECM), and AMD3100 decreased cartilage cleavage. However, in a rat tail disc degeneration model, the injection of SDF‑1 into the NP resulted in the retention of dense areas of proteoglycan matrix and enhanced NP regeneration. These results suggest that SDF‑1, as an inflammatory cytokine, induces MMP expression in human endplate chondrocytes and that ECM remodeling in the CEP may be a favorable factor of endogenous stem cell homing into the NP for regeneration in vivo.

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