title: Insulin-like growth factor-1 boosts the developing process of condylar hyperplasia by stimulating chondrocytes proliferation.
abstract: OBJECTIVE
  The etiology of Condylar hyperplasia (CH) of human temporomandibular joint (TMJ) remains largely unknown. 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 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 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, as 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.
authors.affiliation: Laboratory of Oral Biomedicine, School of Stomatology, Wuhan University, Wuhan, Hubei province, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Ke
authors.forename: X
authors.initials: X
authors.lastname: Long
authors.forename: Q
authors.initials: Q
authors.lastname: Meng
authors.forename: M
authors.initials: M
authors.lastname: Deng
authors.forename: W
authors.initials: W
authors.lastname: Fang
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: H
authors.initials: H
authors.lastname: Cai
authors.forename: S
authors.initials: S
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024043:Collagen Type II / Q000096:biosynthesis / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008335:Mandibular Condyle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008858:Microscopy, Phase-Contrast; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D013704:Temporomandibular Joint / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1