The Biological Response of Human NP Cells to Soluble Collagen VI

Extracellular matrix (ECM) dysregulation plays a significant role in the development of intervertebral disc disease (IVDD). The ECM around the chondrocytes in the nucleus pulposus (NP) is unique in that it contains ColVI. While linked to chondrocyte proliferation in cartilage, ColVI's specific role in IVD degeneration is less clear. Our aim was to determine the expression of ColVI in NP cells from degenerative IVDs, along with the effects of soluble ColVI on NP cells. Thus, we compared the expression levels of ColVI in human degenerated IVD samples, along with the effect of soluble ColVI on primary human NP cells. A higher Pfirrmann grade was associated with increased COL6A1 mRNA expression, with a 4.4-fold increase in Pfirrmann grade IV (p = 0.024) and a 5.3-fold increase in grade V compared to grade III (p = 0.014). Soluble ColVI increased NP cell proliferation compared to untreated controls, from 1.204-fold for 5 µg/mL (p < 0.001) and 1.335-fold for 10 µg/mL (p = 0.001). The most upregulated gene was IGF-1 (7.9-fold increase). Co-treatment of NP cells with ColVI and an ERK inhibitor showed significantly less IGF-1 mRNA upregulation compared to ColVI treatment alone (6.2-fold vs. 12.4-fold; p = 0.009). Our findings suggest that degenerating discs are associated with COL6A1 upregulation by NP cells; moreover, the addition of soluble ColVI to NP cells increases NP cell proliferation and IGF-1 expression.