MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration

Xin Yu; Zheng Li; Jianxiong Shen; William K K Wu; Jinqian Liang; Xisheng Weng; Guixing Qiu

doi:10.1371/journal.pone.0083080

MicroRNA-10b promotes nucleus pulposus cell proliferation through RhoC-Akt pathway by targeting HOXD10 in intervetebral disc degeneration

PLoS One. 2013 Dec 20;8(12):e83080. doi: 10.1371/journal.pone.0083080. eCollection 2013.

Authors

Xin Yu¹, Zheng Li², Jianxiong Shen², William K K Wu³, Jinqian Liang², Xisheng Weng², Guixing Qiu²

Affiliations

¹ 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.
² Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, China.
³ 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.

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.

Publication types

Retracted Publication

MeSH terms

Adult
Cell Proliferation
Chondrocytes / metabolism*
Chondrocytes / pathology
Female
Gene Expression Regulation
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Humans
Intervertebral Disc Degeneration / genetics*
Intervertebral Disc Degeneration / metabolism
Intervertebral Disc Degeneration / pathology
Male
MicroRNAs / genetics*
MicroRNAs / metabolism
Middle Aged
Phosphorylation
Primary Cell Culture
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / genetics*
Proto-Oncogene Proteins c-akt / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction
Spine / metabolism
Spine / pathology
Transcription Factors / genetics*
Transcription Factors / metabolism
rho GTP-Binding Proteins / antagonists & inhibitors
rho GTP-Binding Proteins / genetics*
rho GTP-Binding Proteins / metabolism
rhoC GTP-Binding Protein

Substances

Homeodomain Proteins
MIRN10 microRNA, human
MicroRNAs
RNA, Small Interfering
Transcription Factors
HOXD10 protein, human
Proto-Oncogene Proteins c-akt
RHOC protein, human
rho GTP-Binding Proteins
rhoC GTP-Binding Protein

Grants and funding

This work was supported by National Natural Science Foundation of P.R. China (Grant Number: 81272053,81330044, and 81301596). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.