Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation

Area of Science:

• Cell Biology
• Stem Cell Biology
• Obesity Research

Background:

• Adipose tissue expansion in obesity involves adipocyte hyperplasia and hypertrophy.
• Adipocytes originate from mesenchymal stem cells (MSCs) via adipogenesis.
• Factors controlling MSC proliferation during adipogenesis are not fully understood.

Purpose of the Study:

• To identify the molecular target of bone morphogenetic protein 3 (Bmp3) in stimulating MSC proliferation.
• To investigate the role of WNT1-inducible signaling pathway protein 1 (Wisp1) in Bmp3-mediated MSC proliferation.

Main Methods:

• DNA microarray analysis to identify Bmp3-regulated genes in MSCs.
• Quantitative analysis of Wisp1 expression following Bmp3 treatment.
• Assessment of MSC proliferation using [(3)H]-thymidine incorporation.
• siRNA-mediated knockdown of Wisp1 to evaluate its role in Bmp3-induced proliferation.

Main Results:

• Bmp3 treatment upregulated Wisp1 expression by 3.7-fold in MSCs.
• Increased Wisp1 expression preceded Bmp3-induced MSC proliferation.
• Recombinant Wisp1 dose-dependently increased MSC proliferation (up to 300%).
• Wisp1 knockdown attenuated Bmp3-stimulated MSC proliferation.

Conclusions:

• Wisp1 is a novel molecular target of Bmp3.
• The Bmp3/Wisp1 signaling pathway plays a significant role in regulating MSC proliferation.
• This pathway is important for adipogenesis and may contribute to obesity.