title: Role of SHOX2 in the development of intervertebral disc degeneration.
abstract: Intervertebral disc (IVD) degeneration is the most common cause of low back pain, which affect 80% of the population during their lives, with heavy economic burden. Many factors have been demonstrated to participate in IVD degeneration. In this study, we investigated the role of short stature homeobox 2 (SHOX2) in the development of IVD degeneration. First, we detected the expression of SHOX2 in different stages of human IVD degeneration; then explored the role of SHOX2 on nucleus pulposus (NP) cells proliferation and apoptosis, finally we evaluated the effect of SHOX2 on the production of extracellular matrix in NP cells. Results showed that the expression of SHOX2 is mainly in NP compared with AF tissues, its expression decreased with the severity of human IVD degeneration. TNF-α treatment led to dose- and time-dependent decrease in SHOX2 mRNA, protein expression and promoter activity in NP cells. The silencing of SHOX2 inhibited NP cells proliferation and induced NP cells apoptosis. Finally, SHOX2 silencing led to decreased aggrecan and collagen II expression, along with increased ECM degrading enzymes MMP3 and ADAMTS-5 in NP cells. In summary, our results indicated that SHOX2 plays an important role in the process of IVD degeneration, and might be a protective factor for IVD degeneration. Further studies are required to confirm its exact role, and clarify the mechanism. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1047-1057, 2017.
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, P.R. China.
authors.forename: Fubiao
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, P.R. China.
authors.forename: Zhaomin
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, P.R. China.
authors.forename: Peiheng
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, P.R. China.
authors.forename: Shilabant Sen
authors.initials: SS
authors.lastname: Sribastav
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, P.R. China.
authors.forename: Huafeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, P.R. China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Spine Surgery, First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Second Road, Guangzhou, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics and Traumatology, The University of Hong Kong, 21 Sassoon Road, Hong Kong, P.R. China.
authors.forename: Victor Y L
authors.initials: VYL
authors.lastname: Leung
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D055959:Intervertebral Disc Degeneration / Q000378:metabolism*; D000070614:Nucleus Pulposus / Q000378:metabolism*; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C484664:SHOX2 protein, human; C109465:Shox2 protein, rat; D014409:Tumor Necrosis Factor-alpha
keywords: SHOX2 gene; TNF-α; intervertebral disc degeneration