【Abstract】 Objective To investigate the biological effects of adenovirusmediated GDF5 (AdGDF5) on extracellular matrix (ECM) expression in human degenerative disc nucleus pulposus (NP) cells, and explore a candidate gene therapy method for intervertebral disc degeneration (IDD). Methods NP cells were isolated, cultured, and then infected by the optimal multiplicity of infection (MOI) of AdGDF5 were set up as experimental group (GDF5 group), and compared with blank control group (Control group) and AdGFP control group (GFP group). The extracellular matrix expressions of NP cells were evaluated at 3, 7, 14 or 21days. The contents of sulfated glycosaminoglycan (sGAG) and hydroxyproline (Hyp) in NP cells were measured. The expression of aggrecan, typeII collagen and proteoglycan were observed respectively by immunofluorescent staining, immunohistochemical staining and SafranineO staining. The transcriptions of aggrecan and collagen II mRNA were analyzed by realtime quantitative polymerase chain reaction (Real timePCR). Results The contents of sGAG and Hyp in NP cells gradually increased following cells culture in all three groups. The GDF5 group exhibited a significantly higher sGAG/DNA than GFP and Control groups on 14 or 21 days (P＜0.05), and showed a significantly greater Hyp/DNA than GFP and Control groups on 7, 14 or 21 days (P＜0.05), whereas GFP group did not show a greater effect than Control group (P＞0.05). The NP cells were stained for aggrecan (Immunofluorescent staining), typeII collagen (Immunohistochemical staining) and proteoglycan (SafranineO staining). The NP cells infected by GDF5 exhibited robust staining on 14 or 21 days, and weakly staining intensity either GFP or Control group. Levels of RNA transcripts for aggrecan and collagen II expression patterns were determined in NP cells using realtime PCR. Compared with GFP or Control groups, GDF5treated group had a significantly upregulated aggrecan and collagen II expression levels on 14 or 21 days point (P＜0.05), whereas GFP group did not demonstrate a significant enhancement than Control group (P＞0.05). Conclusion AdGDF5 could obviously upregulate aggrecan and collagen II mRNA transcription in NP cells and increase the synthesis of proteoglycan and typeII collagen. AdGDF5 could restore the extracellular matrix of degenerated NP cells and could be a potential candidate method of gene therapy for IDD.