Long non-coding RNA DANCR modulates osteogenic differentiation by regulating the miR-1301-3p/PROX1 axis

Area of Science:

• Molecular Biology
• Stem Cell Biology
• Bone Biology

Background:

• Bone health relies on balancing osteoblasts and marrow adipocytes derived from bone marrow mesenchymal stem cells (BM-MSCs).
• Dysregulation favoring adipogenesis over osteogenesis in BM-MSCs contributes to osteoporosis, particularly under aging or pathological conditions.
• The precise mechanism of long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) in human BM-MSC osteogenic differentiation remains incompletely understood.

Purpose of the Study:

• To elucidate the regulatory mechanism of DANCR in human BM-MSC osteogenic differentiation.
• To investigate the interplay between DANCR, miR-1301-3p, and PROX1 in the context of osteogenesis.

Main Methods:

• Quantitative analysis of DANCR, miR-1301-3p, and PROX1 expression during human BM-MSC osteogenic differentiation.
• Overexpression and silencing of DANCR in human BM-MSCs followed by assessment of osteogenic markers (ALP, RUNX2, osteocalcin, Osterix).
• Investigation of the sponging interaction between DANCR and miR-1301-3p, and the subsequent effect on PROX1 expression.
• Functional rescue experiments involving miR-1301-3p and PROX1 modulation to confirm their roles in DANCR-mediated osteogenesis.

Main Results:

• DANCR and PROX1 expression decreased, while miR-1301-3p increased during human BM-MSC osteogenic differentiation.
• DANCR overexpression inhibited osteogenic differentiation, evidenced by reduced marker expression, whereas DANCR silencing promoted it.
• DANCR directly sponged miR-1301-3p, leading to the regulation of PROX1 expression.
• Overexpression of miR-1301-3p reversed DANCR's inhibitory effect, and PROX1 elevation counteracted miR-1301-3p's promoting effect on osteogenesis.

Conclusions:

• DANCR suppresses human BM-MSC osteogenic differentiation through the miR-1301-3p/PROX1 axis.
• This study reveals a novel molecular mechanism by which DANCR influences osteogenesis, offering potential therapeutic targets for osteoporosis.