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

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.

Neural crest delamination and migration: Looking forward to the next 150 years

“…Although it was not tested in this work, one expects that chemotaxis towards Sdf1 would be affected too. Interestingly, hypoxia is known to activate PDGFRα expression in smooth muscle cells (Aversa et al, ) and Cx43 is one of the PDGF signaling target in these cells (Zhang et al, ). Therefore, it is possible that, in Xenopus cephalic NC cells, the regulation of N‐cadherin is also linked to Hif1α via PDGF and Cx43.…”

“…Further, MMP14 regulates fibronectin turnover and degradation (Shi & Sottile, ). Furthermore, Sdf1/Cxcr4 signaling is known to activate expression of several MMPs including MMP1, 2, 3, 9, 13, and 14 (Gravina et al, ; Rafii et al, ; Zhang, Zhu, Zhang, & Wu, ). Therefore, MMP14 could be used to first release latent Sdf1 bound to fibronectin.…”

Serum CXCL12/SDF-1 level is positively related with lumbar intervertebral disc degeneration and clinical severity

“…20 CXCL12 has also been shown to accelerate the degradation of the extracellular matrix (ECM) and increase MMP expression in human disc endplate chondrocytes. 21 In addition, using the NF-jB pathway, the CXCL12/CXCR4 axis can cause apoptosis of human degenerative nucleus pulposus cells. 22 All these results imply that CXCL12 may be an important factor involved in IDD progression.…”

Granulocyte‐colony stimulating factor improves intervertebral disc degeneration in experimental adult male rats: A microscopic and radiological study

“…Thus, SDF‐1 is overexpressed in the degenerated IVD tissue, meaning CD34+ progenitor cells will undergo a process of chemotactic attraction toward this gradient from the peripheral blood to the injured site (Henry, Clouet, Le Bideau, Le Visage, & Guicheux, 2018; Zhao et al, 2017). Therefore, SDF‐1‐associated inflammation that can lead to the degeneration or remodeling of the extracellular matrix in endplate cartilage could enhance the migration of exogenous stem cells toward the NP (Zhang, Zhu, Zhang, & Wu, 2018).…”