title: 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.
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
authors.forename: Hehai
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, Guangdong, China.
authors.forename: Kuibo
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
authors.forename: Zemin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism*; D000070614:Nucleus Pulposus / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats
chemical_list: D016328:NF-kappa B
keywords: JNK; NF-κB; extracellular matrix; hypoxia; nucleus pulposus