Abstract
BackgroundUnderstanding the molecular basis underlying the formation of bone-forming osteocytes and lipid-storing adipocytes will help provide insights into the cause of disorders originating in stem/progenitor cells and develop therapeutic treatments for bone- or adipose-related diseases. In this study, the role of RGS2 and RGS4, two members of the regulators of G protein signaling (RGS) family, was investigated during adipogenenic and osteogenenic differentiation of human mesenchymal stem cells (hMSCs).ResultsExpression of RGS2 and RGS4 were found to be inversely regulated during adipogenesis induced by dexamethasone (DEX) and 3-isobutyl-methylxanthine, regardless if insulin was present, with RGS2 up-regulated and RGS4 down-regulated in response to adipogenic induction. RGS2 expression was also up-regulated during osteogenesis at a level similar to that induced by treatment of DEX alone, a shared component of adipogenic and osteogenic differentiation inducing media, but significantly lower than the level induced by adipogenic inducing media. RGS4 expression was down-regulated during the first 48 h of osteogenesis but up-regulated afterwards, in both cases at levels similar to that induced by DEX alone. Expression knock-down using small interfering RNA against RGS2 resulted in decreased differentiation efficiency during both adipogenesis and osteogenesis. On the other hand, expression knock-down of RGS4 also resulted in decreased adipogenic differentiation but increased osteogenic differentiation.ConclusionsRGS2 and RGS4 are differentially regulated during adipogenic and osteogenic differentiation of hMSCs. In addition, both RGS2 and RGS4 play positive roles during adipogenesis but opposing roles during osteogenesis, with RGS2 as a positive regulator and RGS4 as a negative regulator. These results imply that members of RGS proteins may play multifaceted roles during human adipogenesis and osteogenesis to balance or counterbalance each other’s function during those processes.
Highlights
Understanding the molecular basis underlying the formation of bone-forming osteocytes and lipidstoring adipocytes will help provide insights into the cause of disorders originating in stem/progenitor cells and develop therapeutic treatments for bone- or adipose-related diseases
Using adipose tissue derived human mesenchymal stem cells (hMSCs) as an in vitro model for adipogenic differentiation, we identified through microarray analysis two members of the regulator of G protein signaling (RGS) family, RGS2 and RGS4, which were differentially regulated upon adipogenic induction
Characterization of adipose‐derived hMSCs by clonogenicity and molecular marker expression The adipose-derived hMSCs used in this study were obtained from a commercial source
Summary
Understanding the molecular basis underlying the formation of bone-forming osteocytes and lipidstoring adipocytes will help provide insights into the cause of disorders originating in stem/progenitor cells and develop therapeutic treatments for bone- or adipose-related diseases. Advancement in understanding adipose and bone tissue biology will help develop new strategies for the prevention and intervention of adipose- and bone-related diseases, including obesity and osteoporosis. Many signaling pathways including TGFβ/BMP signaling, Wnt signaling, HH signaling, Notch signaling, PI3K signaling, and ERK1/2 and p38 MAPK mediated signaling, as well as growth factors (FGFs), hormones (Estrogen and Parathyroid hormone), transcription factors (Runx and Osterix), bone matrix proteins (ALP, BSP, OCN, OPN, COL 1) and microRNAs etc. Runx regulates the expression of osteogenic markers ALP, BSP, OCN, OPN and COL 1, as well as Osterix, though Osterix can be induced by signaling pathways independent of Runx2 [16]
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