Inhibition of actin polymerization decreases osteogeneic differentiation of mesenchymal stem cells through p38 MAPK pathway.
BACKGROUND
Mesenchymal Stem Cells (MSC) are important candidates for therapeutic applications due to their ex vivo proliferation and differentiation capacity. MSC differentiation is controlled by both intrinsic and extrinsic factors and actin cytoskeleton plays a major role in the event. In the current study, we tried to understand the initial molecular mechanisms and pathways that regulate the differentiation of MSC into osteocytes or adipocytes.


RESULTS
We observed that actin modification was important during differentiation and differentially regulated during adipogenesis and osteogenesis. Initial disruption of actin polymerization reduced further differentiation of MSC into osteocytes and osteogenic differentiation was accompanied by increase in ERK1/2 and p38 MAPK phosphorylation. However, only p38 MAPK phosphorylation was down regulated upon inhibition of actin polymerization which as accompanied by decreased CD49E expression.


CONCLUSIONS
Taken together, our results show that actin modification is a pre-requisite for MSC differentiation into osteocytes and adipocytes and osteogenic differentiation is regulated through p38 MAPK phosphorylation. Thus by modifying their cytoskeleton the differentiation potential of MSC could be controlled which might have important implications for tissue repair and regeneration.
Stem Cell and Cancer Biology Group, Indian Institute of Technology Guwahati, Guwahati, Assam, India. bithiahgj@iitg.ernet.in.
Himangshu
H
Sonowal
Atul
A
Kumar
Jina
J
Bhattacharyya
Pabitra Kumar
PK
Gogoi
Bithiah Grace
BG
Jaganathan
D008841:Actin Cytoskeleton / Q000737:chemistry*; D000199:Actins / Q000737:chemistry; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis; D002454:Cell Differentiation; D015638:Cytochalasin D / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D020935:MAP Kinase Signaling System; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis; D058105:Polymerization
D000199:Actins; D015638:Cytochalasin D