Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells

Lei Zhang,Liwu Zhou,Shuo Chen,Ben Shi,Jianning Zhao,Xiangyi Sun,Chao Yang

doi:10.1042/bsr20170347

Abstract

miRNAs have been reported to regulate cellular differentiation by modulating multiple signaling pathways. Long noncoding RNA (lnc RNA) DANCR was previously identified to be critical for the chondrogenesis of human synovium-derived mesenchymal stem cells (SMSC), however, the underlying molecular mechanism requires better understanding. Here, miRNA expression profiling in DANCR overexpressed in SMSCs identified significant down-regulation of miR-1305, which serves as a downstream target of DANCR. Notably, miR-1305 overexpression reversed DANCR-induced cell proliferation and chondrogenic differentiation of SMSCs, which suggested that miR-1305 antagonized the function of DANCR. Mechanistically, highly expressed miR-1305 resulted in the decreased expression of the TGF-β pathway member Smad4, and inhibition of miR-1305 enhanced the expression level of Smad4. Depletion of Smad4 suppressed the promotion of DANCR in cell proliferation and chondrogenesis of SMSCs. Collectively, our results characterized miR-1305-Smad4 axis as a major downstream functional mechanism of lncRNA DANCR in promoting the chondrogenesis in SMSCs.

Highlights

Osteoarthritis is a chronic, progressive, and degenerative form of arthritis, which remains a major clinical challenge due to the limited self-repair capacity of cartilage
Amongst the various available sources, mesenchymal stem cell (MSC) seem to have many advantages over their counterparts, while recent study demonstrated that synovium-derived MSCs (SMSCs), which have better chondrogenic potential compared with MSC, are gaining momentum [12,13,14,15,16,17].Improved MRI features, histology, and better clinical outcome have been achieved in cartilage repair derived from synovium-derived mesenchymal stem cells (SMSC) [14]
As cell proliferation is tightly associated with cell cycle progression, the cell cycle distribution of SMSCs harboring control vector or DANCR was monitored by FACS analysis

Summary

Introduction

Osteoarthritis is a chronic, progressive, and degenerative form of arthritis, which remains a major clinical challenge due to the limited self-repair capacity of cartilage. Amongst the various available sources, MSCs seem to have many advantages over their counterparts, while recent study demonstrated that synovium-derived MSCs (SMSCs), which have better chondrogenic potential compared with MSC, are gaining momentum [12,13,14,15,16,17].Improved MRI features, histology, and better clinical outcome have been achieved in cartilage repair derived from SMSCs [14]. These findings shed light on the potential application of SMSC in the field of chondrogenesis, and understanding the molecular mechanism in cartilage repair will benefit the use of SMSCs

Methods

Results

Conclusion