Regulation of chondrocyte proliferation through GIT1-Rac1-mediated ERK1/2 pathway by PDGF

Jin Xiao; Xuqiong Chen; Lipeng Xu; Ying Zhang; Qingshui Yin; Fei Wang

doi:10.1002/cbin.10241

Regulation of chondrocyte proliferation through GIT1-Rac1-mediated ERK1/2 pathway by PDGF

Cell Biol Int. 2014 Jun;38(6):695-701. doi: 10.1002/cbin.10241. Epub 2014 Feb 10.

Authors

Jin Xiao¹, Xuqiong Chen, Lipeng Xu, Ying Zhang, Qingshui Yin, Fei Wang

Affiliation

¹ Department of Orthopedics, Liuhuaqiao Hospital, Guangzhou, 510010, People's Republic of China.

PMID: 24420748
DOI: 10.1002/cbin.10241

Abstract

There are many growth factors contributing to fracture healing after bone fractures. Platelet-derived growth factor (PDGF) released from platelets is a factor promoting cell division and proliferation, and first appears around the sites of fractures. Culture of chondrocytes in vitro are stimulated by PDGF to proliferation, its presence being upregulated in the extracellular matrix of cartilage; the main components include aggrecan and type II collagen. PDGF induces the expression of G the protein-coupled receptor kinase interacting protein 1 (GIT1), promoting Rac1 and ERK1/2 phosphorylation. Both knocking down GIT1 expression by siRNA and blocking phosphorylation of Rac1 inhibit this induced proliferation of chondrocyte. GIT1 and Rac1 control each other, having a synergistic effect on activation of the ERK1/2 pathway. The results suggest that PDGF regulates chondrocyte proliferation through activation of ERK1/2 pathway by upregulation of GIT1 expression and Rac1 phosphorylation.

Keywords: ERK1/2; GIT1; PDGF; Rac1; chondrocyte.

MeSH terms

Aminoquinolines / pharmacology
Animals
Cell Cycle Proteins / biosynthesis*
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Proliferation
Cells, Cultured
Chondrocytes / physiology
Flavonoids / pharmacology
Fractures, Bone
G1 Phase Cell Cycle Checkpoints
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / metabolism*
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / metabolism*
Phosphoproteins / biosynthesis*
Phosphoproteins / genetics
Phosphoproteins / metabolism
Phosphorylation
Platelet-Derived Growth Factor / metabolism*
Pyrimidines / pharmacology
RNA Interference
RNA, Small Interfering
Rats
Rats, Sprague-Dawley
Wound Healing
rac1 GTP-Binding Protein / antagonists & inhibitors
rac1 GTP-Binding Protein / metabolism*

Substances

Aminoquinolines
Cell Cycle Proteins
Flavonoids
Git1 protein, rat
NSC 23766
Phosphoproteins
Platelet-Derived Growth Factor
Pyrimidines
RNA, Small Interfering
platelet-derived growth factor A
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Rac1 protein, rat
rac1 GTP-Binding Protein
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one