Hypoxia suppresses serum deprivation-induced degradation of the nucleus pulposus cell extracellular matrix through the JNK and NF-κB pathways

Abstract

Intervertebral disc (IVD) degeneration is associated with the imbalance between anabolism and catabolism of the nucleus pulposus (NP) extracellular matrix (ECM). Serum deprivation (SD) has been reported to exacerbate IVD degeneration; however, the effect of SD on ECM metabolism is not fully understood. Hypoxia plays important roles in maintaining the physiological functions of IVD cells; however, whether hypoxia has any effect on NP ECM production under conditions of SD is still unclear. In the current study, we established an in vitro SD model by exposing NP cells to serum-free medium. SD decreased the expression of aggrecan and collagen II, as well as the production of sulfated glycosaminoglycan (sGAG) in a time-dependent manner. However, hypoxia abolished SD-mediated down-regulation of aggrecan and collagen II expression via JNK1/2 activation. Moreover, hypoxia abolished SD-induced MMP-3 and MMP-13 expression by inhibiting NF-κB activation, p65 translocation, and MMP-3 and MMP-13 promoter activity. These results indicated that, hypoxia maintained ECM production under conditions of SD. This effect was elicited in part through JNK1/2-mediated up-regulation of matrix gene expression and down-regulation of MMP expression, through the inhibition of NF-κB. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2059–2066, 2017.