Objective      To investigate the effects of bone morphogenetic protein 9 (BMP9) on inflammatory response and apoptosis of degenerative nucleus pulposus cells and to mechanistically explore its association with PI3K/Akt signaling pathway.  Methods      The degenerative nucleus pulposus cells were generated by oxygen glucose deprivation (OGD) method. BMP9 gene was transinduced into human nucleus pulposus cells (HNPCs) by recombinant adeno-associated virus (AAV) mediated gene transfer. According to the transfection and treatment

HNPCs were divided into 5 groups: Control group (cultured HNPCs without treatment)

OGD group (OGD model)

AAV group (OGD+AAV empty vector)

AAV-BMP9 group (OGD+AAV-BMP9)

and AAV-BMP9+LY294002 group (OGD+AAV-BMP9+PI3K inhibitor LY294002). Immunofluorescence staining was used to detect Aggrecan and type Ⅱ collagen (Col2a1). Western blot were performed to detect the protein expression of p-Akt and p-mTOR. Enzyme linked immunosorbent assay (ELISA) was carried out to measure the levels of TNF-α

IL-1β

IL-6 and IL-8 in the supernatant of medium. Flow cytometry was performed to detect cell apoptosis.  Results       The expression of Aggrecan and Col2a1 was significantly decreased in OGD model. The protein expression of p-Akt and p-mTOR was higher in AAV-BMP9 group than those in OGD and AAV groups (P0-.05). In addition

the levels of TNF-α

IL-1β

IL-6 and IL-8 were significantly decreased (P0.05) and cell apoptosis was markedly reduced in HNPCs of AAV-BMP9 group. But

LY294002 treatment significantly reversed the above-mentioned effects induced by BMP9 overexpression in degenerative HNPCs.    Conclusion       BMP9 inhibits the inflammatory response and apoptosis of degenerative HNPCs through activating PI3K/Akt signaling pathway.