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lncRNA SNHG1 attenuates osteogenic differentiation via the miR‑101/DKK1 axis in bone marrow mesenchymal stem cells

Jie Xiang1, Hai-Qing Fu2, Zhun Xu2

  • 1Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Molecular Medicine Reports
|September 9, 2020
PubMed

Insights

Long non-coding RNA SNHG1 inhibits bone mesenchymal stem cell differentiation, potentially offering a new therapeutic target for osteoporosis. This study uncovers the miR-101/DKK1 pathway

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Osteoporosis (OP) is linked to impaired bone mesenchymal stem cell (BMSC) osteogenic differentiation.
  • The precise regulatory mechanisms governing this process, particularly involving long non-coding RNAs (lncRNAs), remain incompletely understood.
  • Identifying novel therapeutic targets for OP is crucial.

Purpose of the Study:

  • To investigate the regulatory role of lncRNA small nucleolar RNA host gene 1 (SNHG1) in BMSC osteogenic differentiation.
  • To elucidate the molecular mechanism by which SNHG1 influences osteogenesis, focusing on its interaction with microRNA (miR)-101 and Dickkopf-1 (DKK1).
  • To explore the potential of targeting the SNHG1/miR-101/DKK1 axis for OP treatment.

Main Methods:

  • Quantitative reverse transcription PCR (RT-qPCR) to measure gene expression (SNHG1, DKK1, miR-101, RUNX2, OPN, OCN).
  • Western blotting to analyze protein expression levels (DKK1, β-catenin, RUNX2, OPN, OCN, osterix, collagen type I α1).
  • Functional assays including alkaline phosphatase activity, Alizarin Red staining, bioinformatics analysis, and luciferase assays to validate interactions and assess osteoblastic phenotype.

Main Results:

  • SNHG1 expression decreased in a time-dependent manner during osteogenic differentiation.
  • Overexpression of SNHG1 significantly inhibited BMSC osteogenic differentiation.
  • SNHG1 was found to directly interact with miR-101 and regulate the Wnt/β-catenin signaling pathway via the miR-101/DKK1 axis, thereby inhibiting osteogenic differentiation.

Conclusions:

  • lncRNA SNHG1 acts as a competitive endogenous RNA (ceRNA) to attenuate BMSC osteogenic differentiation.
  • The inhibitory effect of SNHG1 on osteogenesis is mediated through the miR-101/DKK1 axis.
  • This study enhances the understanding of lncRNA-mediated regulation in osteogenic differentiation and suggests SNHG1 as a potential therapeutic target for osteoporosis.

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