Background. Signalling by growth differentiation factor 6 (GDF6/BMP13) has been implicated in the development and maintenance of healthy NP cell phenotypes and GDF6 mutations are associated with defective vertebral segmentation in Klippel-Feil syndrome. GDF6 may thus represent a promising biologic for treatment of IVD degeneration. This study aimed to investigate the effect of GDF6 in human NP cells and critical signal transduction pathways involved. Methods. BMP receptor expression profile of non-degenerate and degenerate human NP cells was determined through western blot, immunofluorescence and qPCR. Phosphorylation statuses of Smad1/5/9 and non-canonical p38 MAPK and Erk1/2 were assessed in the presence/absence of pathway blockers. NP marker and matrix degrading enzyme gene expression was determined by qPCR following GDF6 stimulation. Glycosaminoglycan and collagen production were assessed through DMMB-assay and histochemical staining. Results. NP cells expressed all GDF6 receptor subunits, with receptor subunits BMPR-1A and BMPR2 displaying the highest expression and highest binding affinity. GDF6 stimulation significantly upregulated the expression of NP specific marker genes but had no significant effect on the expression of matrix degrading enzymes. Total glycosaminoglycan and collagen production was also significantly increased following GDF6 stimulation. Smad1/5/9, p38 MAPK and Erk1/2 pathways were phosphorylated following GDF6 stimulation and could be effectively blocked. Conclusions. These findings enhance our understanding of both the effects of GDF6 in NP cells and the mechanisms of GDF6 signal transduction that are critical to promote NP phenotype and cellular function. This knowledge is important for the effective use of GDF6 as a therapeutic molecule for treatment of IVD degeneration. Conflicts of interest. No conflicts of interest. Sources of funding. We would like to acknowledge UKRMP Acellular Hub, MRC, NIHR Musculoskeletal BRU and The Rosetrees Trust for funding this research

Aims

This study, using a surgeon-maintained database, aimed to explore the risk factors for surgery-related complications in patients undergoing primary cervical spine surgery for degenerative diseases.