title: MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration.
abstract: Aberrant proliferation of nucleus pulposus cell is implicated in the pathogenesis of intervertebral disc degeneration. Recent findings revealed that microRNAs, a class of small noncoding RNAs, could regulate cell proliferation in many pathological conditions. Here, we showed that miR-10b was dramatically upregulated in degenerative nucleus pulposus tissues when compared with nucleus pulposus tissues isolated from patients with idiopathic scoliosis. Moreover, miR-10b levels were associated with disc degeneration grade and downregulation of HOXD10. In cultured nucleus pulposus cells, miR-10b overexpression stimulated cell proliferation with concomitant translational inhibition of HOXD10 whereas restored expression of HOXD10 reversed the mitogenic effect of miR-10b. MiR-10b-mediated downregulation of HOXD10 led to increased RhoC expression and Akt phosphorylation. Either knockdown of RhoC or inhibition of Akt abolished the effect of miR-10b on nucleus pulposus cell proliferation. Taken together, aberrant miR-10b upregulation in intervertebral disc degeneration could contribute to abnormal nucleus pulposus cell proliferation through derepressing the RhoC-Akt pathway by targeting HOXD10. Our study also underscores the potential of miR-10b and the RhoC-Akt pathway as novel therapeutic targets in intervertebral disc degeneration.
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China ; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beilishi Road, Xicheng District, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Institute of Digestive Disease and State Key Laboratory of Digestive Disease, LKS Institute of Health Sciences & Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong.
authors.forename: William K K
authors.initials: WK
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Jinqian
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Weng
authors.affiliation: Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
authors.forename: Guixing
authors.initials: G
authors.lastname: Qiu
mesh_terms: D000328:Adult; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010766:Phosphorylation; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013131:Spine / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
chemical_list: D018398:Homeodomain Proteins; C547183:MIRN10 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D014157:Transcription Factors; C072064:HOXD10 protein, human; D051057:Proto-Oncogene Proteins c-akt; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein