title: IGF1 regulates RUNX1 expression via IRS1/2: Implications for antler chondrocyte differentiation.
abstract: Although IGF1 is important for the proliferation and differentiation of chondrocytes, its underlying molecular mechanism is still unknown. Here we addressed the physiologic function of IGF1 in antler cartilage and explored the interplay of IGF1, IRS1/2 and RUNX1 in chondrocyte differentiation. The results showed that IGF1 was highly expressed in antler chondrocytes. Exogenous rIGF1 could increase the proliferation of chondrocytes and cell proportion in the S phase, whereas IGF1R inhibitor PQ401 abrogated the induction by rIGF1. Simultaneously, IGF1 could stimulate the expression of IHH which was a well-known marker for prehypertrophic chondrocytes. Further analysis evidenced that IGF1 regulated the expression of IRS1/2 whose silencing resulted in a rise of IHH mRNA levels, but the regulation was impeded by PQ401. Knockdown of IRS1 or IRS2 with specific siRNA could greatly enhance rIGF1-induced chondrocyte differentiation and reduce the expression of RUNX1. Extraneous rRUNX1 might rescue the effects of IRS1 or IRS2 siRNA on the differentiation. In antler chondrocytes, IGF1 played a role in modulating the expression of RUNX1 through IGF1R. Moreover, attenuation of RUNX1 expression advanced the differentiation elicited by rIGF1, while administration of rRUNX1 to chondrocytes treated with IGF1 siRNA or PQ401 reduced their differentiation. Additionally, siRNA-mediated downregulation of IRS1 or IRS2 in the chondrocytes impaired the interaction between IGF1 and RUNX1. Collectively, IGF1 could promote the proliferation and differentiation of antler chondrocytes. Furthermore, IRS1/2 might act downstream of IGF1 to regulate chondrocyte differentiation through targeting RUNX1.
authors.affiliation: a College of Veterinary Medicine, Jilin University , Changchun , P. R. China.
authors.forename: Zhan-Qing
authors.initials: ZQ
authors.lastname: Yang
authors.affiliation: a College of Veterinary Medicine, Jilin University , Changchun , P. R. China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Zhang
authors.affiliation: b Institute of Agro-food Technology, Jilin Academy of Agricultural Sciences , Changchun , P. R. China.
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Duan
authors.affiliation: a College of Veterinary Medicine, Jilin University , Changchun , P. R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Geng
authors.affiliation: a College of Veterinary Medicine, Jilin University , Changchun , P. R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: a College of Veterinary Medicine, Jilin University , Changchun , P. R. China.
authors.forename: Hai-Fan
authors.initials: HF
authors.lastname: Yu
authors.affiliation: a College of Veterinary Medicine, Jilin University , Changchun , P. R. China.
authors.forename: Zhan-Peng
authors.initials: ZP
authors.lastname: Yue
authors.affiliation: a College of Veterinary Medicine, Jilin University , Changchun , P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
mesh_terms: D000818:Animals; D000999:Antlers / Q000166:cytology*; D002356:Cartilage / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics* / Q000378:metabolism; D003670:Deer; D005786:Gene Expression Regulation; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D055504:Insulin Receptor Substrate Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I
keywords: IGF1; IRS1/2; RUNX1; antler; chondrocyte; differentiation