Collagen-Derived Peptide N-Acetylated Proline-Glycine-Proline in Intervetebral Disc Recruits Cartilage Endplate Stem Cells by Binding with CXC Receptor 2

Abstract

Introduction Degenerative disc disease (DDD) is a prevalent musculoskeletal disorder and is the major cause of low back pain. But our comprehension about development of the intervertebral disc (IVD) and pathogenesis of disc degeneration is unclear, which is an obstacle for appropriate therapies. Recently, some reports identified stem/progenitor cells within particular IVD niches and cartilage endplate. These cells together with mesenchymal stem cells (MSC) are recruited to nucleus pulposus(NP) and annulus fibrosus(AF) to generate regenerative functions in a healthy IVD. The possibility of stimulating these stem cells holds promise for future therapy for DDD. But factors which recruit stem cells to NP and AF are unknown. There are increasing evidences that N-acetylated proline-glycine-proline (N-AC-PGP), which is a degradation fragment of collagen, plays an important role in inflammatory cell recruitment. But whether it presents in IVD and whether it is a chemokine of stem cell have remained elusive. Materials and Methods In this study, we detected the presence of N-AC-PGP by liquid chromatography-mass spectrum in IVD with different degeneration grade and the enzymes responsible for generating N-AC-PGP, matrix metalloproteases 8 and 9 and prolyl endopeptidase (PE), are also quantified by ELISA in these IVD samples. To found out the role of N-AC-PGP in IVD, cartilage endplate stem cells (CESC) chemotaxis assay was performed by Tanswell assay. Results We demonstrate the correlation between N-AC-PGP content in IVD and content of MMP-8and9 and PE.N-AC-PGP increase with increasing degeneration grade of IVD. Then, we described the generation pathway of N-AC-PGP in IVD. Finally, we demonstrated that N-AC-PGP can recruit CESC by binding with CXC receptors 2 on CESC. Conclusion These findings reveal a possible regeneration mechanism in IVD, which depends on the chemotaxis of N-AC-PGP for CESC and indicate a new therapy by using N-AC-PGP to stimulate stem cells in IVD. Disclosure of Interest None declared References Snelgrove RJ, Jackson PL, Hardison MT, et al. A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation. Science 2010;330(6000):90–94 Gaggar A, Jackson PL, Noerager BD, et al. A novel proteolytic cascade generates an extracellular matrix-derived chemoattractant in chronic neutrophilic inflammation. J Immunol 2008;180(8):5662–5669 Weathington NM, van Houwelingen AH, Noerager BD, et al. A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med 2006;12(3):317–323