title: Regulation of chondrocyte proliferation through GIT1-Rac1-mediated ERK1/2 pathway by PDGF.
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.
authors.affiliation: Department of Orthopedics, Liuhuaqiao Hospital, Guangzhou, 510010, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xiao
authors.forename: Xuqiong
authors.initials: X
authors.lastname: Chen
authors.forename: Lipeng
authors.initials: L
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qingshui
authors.initials: Q
authors.lastname: Yin
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D050723:Fractures, Bone; D059585:G1 Phase Cell Cycle Checkpoints; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D018797:Cell Cycle Proteins; D005419:Flavonoids; C485648:Git1 protein, rat; C487513:NSC 23766; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D011743:Pyrimidines; D034741:RNA, Small Interfering; C075278:platelet-derived growth factor A; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
keywords: ERK1/2; GIT1; PDGF; Rac1; chondrocyte