Format

Send to

Choose Destination
Sci Rep. 2018 Jun 15;8(1):9225. doi: 10.1038/s41598-018-27514-x.

The microRNA-10a/ID3/RUNX2 axis modulates the development of Ossification of Posterior Longitudinal Ligament.

Author information

1
Spine Center, Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003, P.R. China.
2
Department of Orthopedic Surgery, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, 800th Yi Shan Road, Shanghai, 200233, P.R. China.
3
Administration Office for Graduate Students, Changhai Hospital, Second Military Medical University, 168th Chang Hai Road, Shanghai, 200433, P.R. China.
4
Research Center of Developmental Biology, Second Military Medical University, 800th Xiang Yin Road, Shanghai, 200433, P.R. China. wangyuesmmu@163.com.
5
Spine Center, Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003, P.R. China. liuyangspine@smmu.edu.cn.
6
Spine Center, Department of Orthopaedics, Changzheng Hospital, Second Military Medical University, 415th Feng Yang Road, Shanghai, 200003, P.R. China. yuanwenspine@smmu.edu.cn.

Abstract

Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the development of OPLL. Here, we set out to unveiling the detailed mechanism of those altered OPLL-specific microRNAs. We screened a set of differentially expressed OPLL-specific microRNAs from the previous sequencing data and showed that microRNA-10a actively modulates the ossification of posterior ligament cells in vitro. Using a tissue-engineered scaffold grown from 4-week-old BALB/c homozygous nude mice, we found that altered microRNA-10a expression in posterior ligament cells indeed affected the heterotopic bone formation in vivo. Furthermore, computational analysis showed that the negative ossification regulator ID3 is a functional target gene of microRNA-10a, and its expression was also significantly altered during microRNA-10a modulation both in vitro and in vivo. Also, we have demonstrated that the ossification promoting function of microRNA-10a requires ID3, as ID3 actively inhibits RUNX2. Thus, we identified a critical role for highly altered OPLL-specific microRNA-10a in regulating the development of OPLL by modulating the ID3/RUNX2 axis.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center