title: MicroRNA-15b silencing inhibits IL-1β-induced extracellular matrix degradation by targeting SMAD3 in human nucleus pulposus cells.
abstract: OBJECTIVE
  To determine the role of microRNA-15b (miR-15b) in interleukin-1 beta (IL-1β)-induced extracellular matrix (ECM) degradation in the nucleus pulposus (NP).
  
  
  RESULTS
  MiR-15b was up-regulated in degenerative NP tissues and in IL-1β-stimulated NP cells, as compared to the levels in normal controls (normal tissue specimens from patients with idiopathic scoliosis). Bioinformatics and luciferase activity analyses showed that mothers against decapentaplegic homolog 3 (SMAD3), a key mediator of the transforming growth factor-β signaling pathway, was directly targeted by miR-15b. Functional analysis demonstrated that miR-15b overexpression aggravated IL-1β-induced ECM degradation in NP cells, while miR-15b inhibition had the opposite effects. Prevention of IL-1β-induced NP ECM degeneration by the miR-15b inhibitor was attenuated by small-interfering-RNA-mediated knockdown of SMAD3. In addition, activation of MAP kinase and nuclear factor-κB up-regulated miR-15b expression and down-regulated SMAD3 expression in IL-1β-stimulated NP cells.
  
  
  CONCLUSIONS
  MiR-15b contributes to ECM degradation in intervertebral disc degeneration (IDD) via targeting of SMAD3, thus providing a novel therapeutic target for IDD treatment.
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Kang
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Cao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Huipeng
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Kangcheng
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, First Hospital of Wuhan, Wuhan, 430022, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Hua
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Tu
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China.
authors.forename: Rongjin
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277, Wuhan, 430022, China. zhangyukuncom@126.com.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D000070614:Nucleus Pulposus / Q000166:cytology / Q000473:pathology*; D059748:Proteolysis; D015398:Signal Transduction; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D053583:Interleukin-1beta; C505361:MIRN15 microRNA, human; D035683:MicroRNAs; C497790:SMAD3 protein, human; D051900:Smad3 Protein
keywords: Extracellular matrix degradation; IL-1β; Intervertebral disc degeneration; MicroRNA-15b; Nucleus pulposus; SMAD3