title: Heme oxygenase-1 attenuates IL-1β induced alteration of anabolic and catabolic activities in intervertebral disc degeneration.
abstract: Intervertebral disc degeneration (IDD) is characterized by disordered extracellular matrix (ECM) metabolism, implicating subdued anabolism and enhanced catabolic activities in the nucleus pulposus (NP) of discs. Pro-inflammatory cytokines such as interleukin-1β (IL-1β) are considered to be potent mediators of ECM breakdown. Hemeoxygenase-1 (HO-1) has been reported to participate in cellular anti-inflammatory processes. The purpose of this study was to investigate HO-1 modulation of ECM metabolism in human NP cells under IL-1β stimulation. Our results revealed that expression of HO-1 decreased considerably during IDD progression. Induction of HO-1 by cobalt protoporphyrin IX attenuated the inhibition of sulfate glycosaminoglycan and collagen type II (COL-II) synthesis and ameliorated the reduced expressions of aggrecan, COL-II, SOX-6 and SOX-9 mediated by IL-1β. Induction of HO-1 also reversed the effect of IL-1β on expression of the catabolic markers matrix metalloproteinases-1, 3, 9 and 13. This was combined with inhibition of the activation of mitogen-activated protein kinase signaling. These findings suggest that HO-1 might play a pivotal role in IDD, and that manipulating HO-1 expression might mitigate the impairment of ECM metabolism in NP, thus potentially offering a novel therapeutic approach to the treatment of IDD.
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Rd, Shanghai 200003, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Rd, Shanghai 200003, China.
authors.forename: Changgui
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Rd, Shanghai 200003, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Rd, Shanghai 200003, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Cao
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Rd, Shanghai 200003, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Rd, Shanghai 200003, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
authors.forename: Lianfu
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Rd, Shanghai 200003, China.
authors.forename: Huajiang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Spinal Surgery, Changzheng Hospital, Second Military Medical University, No. 415 Feng Yang Rd, Shanghai 200003, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
mesh_terms: D000328:Adult; D000368:Aged; D053674:Aggrecans / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism*; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D008875:Middle Aged; D000070614:Nucleus Pulposus / Q000378:metabolism / Q000473:pathology; D011524:Protoporphyrins / Q000096:biosynthesis
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D053583:Interleukin-1beta; D011524:Protoporphyrins; C007095:cobaltiprotoporphyrin; D051547:Heme Oxygenase-1; D020782:Matrix Metalloproteinases