Our previous study has demonstrated that enriched insulin-like growth factor-1(IGF-1) was expressed in the proliferation and hypertrophic layers of CH cartilage. Accordingly, this study was aimed to investigate whether IGF-1 regulates CH chondrocytes proliferation in condylar cartilage overgrowth and explore the molecular mechanism of IGF-1 involved in.
Methods: Chondrocytes were isolated from 6 CH and 3 normal cartilage (NC) specimens and cultured in alginate beads or monolayer, treated with IGF-1 or specific inhibitors such as
7-[trans-3-[(azetidin-1-yl)-methyl]cyclobutyl]-5-(3-benzyloxyphenyl)7H-pyrrolo[2,3-d]pyrimidin-4-amine (NVP-AEW541). U0126, and LY294002. Thereafter, cellular proliferation capacity www.selleckchem.com/products/AZD7762.html was evaluated by Cell Viability Analyzer (alginate beads culture) or 3(4,5-dimethylthiazo(-2-yl)-2,5-diphenyltetrazolium bromide (MTT) (monolayer culture). Gene expression levels of IGF-1, IGF-1 receptor (IGF-1R), collagen selleck compound type II, type X and those genes associated with proliferation were evaluated by realtime PCR. Protein levels of IGF-1 and IGF-1R synthesized by CH chondrocytes were accessed by enzyme-linked immunosorbent assay (ELISA) and western blotting.
Results: CH chondrocytes enhanced cellular proliferation capacity and expressed significantly higher levels of messenger RNA (mRNA)
and protein expressions of IGF-1 and IGF-1R, a; compared with NC chondrocytes. Furthermore, enriched IGF-1 enhanced CH chondrocytes proliferation, up-regulated the expressions of specific genes associated with
cellular proliferation and elevated the gene expression of collagen type II A1 (COL2A1). Besides, IGF-1-mediated CH chondrocytes proliferation mainly depended on the mitogen-activated protein kinase (MAPK)-ERK pathway.
Conclusions: IGF-1 promotes human TMJ cartilage overgrowth in the developing process of CH by enhancing chondrocytes proliferation via MAPK-ERK pathway. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.”
“The expression levels of the MYC oncoprotein have long been recognized to be associated with the outputs of major cellular processes including proliferation, cell growth, Baf-A1 apoptosis, differentiation, and metabolism. Therefore, to understand how MYC operates, it is important to define quantitatively the relationship between MYC input and expression output for its targets as well as the higher-order relationships between the expression levels of subnetwork components and the flow of information and materials through those networks. Two different views of MYC are considered, first as a molecular microeconomic manager orchestrating specific positive and negative responses at individual promoters in collaboration with other transcription and chromatin components, and second, as a macroeconomic czar imposing an overarching rule onto all active genes.