title: Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis.
abstract: Granulin epithelin precursor (GEP) has been implicated in development, tissue regeneration, tumorigenesis, and inflammation. Herein we report that GEP stimulates chondrocyte differentiation from mesenchymal stem cells in vitro and endochondral ossification ex vivo, and GEP-knockdown mice display skeleton defects. Similar to bone morphogenic protein (BMP) 2, application of the recombinant GEP accelerates rabbit cartilage repair in vivo. GEP is a key downstream molecule of BMP2, and it is required for BMP2-mediated chondrocyte differentiation. We also show that GEP activates chondrocyte differentiation through Erk1/2 signaling and that JunB transcription factor is one of key downstream molecules of GEP in chondrocyte differentiation. Collectively, these findings reveal a novel critical role of GEP growth factor in chondrocyte differentiation and the molecular events both in vivo and in vitro.
authors.affiliation: Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M University System Health Science Center, Dallas, Texas, USA.
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
authors.forename: Feng-Jin
authors.initials: FJ
authors.lastname: Guo
authors.forename: Bai-Chun
authors.initials: BC
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Sally
authors.initials: S
authors.lastname: Frenkel
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Yixia
authors.initials: Y
authors.lastname: Xie
authors.forename: Chuan-Ju
authors.initials: CJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism*; D002356:Cartilage / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D020219:Chondrogenesis / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D005333:Fetus / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D000077153:Progranulins; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D055396:Bone Morphogenetic Protein 2; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D016755:Proto-Oncogene Proteins c-jun; D015347:RNA Probes; D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3