Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis.
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.
Feng
Jian Q
JQ
Department of Biomedical Sciences, Baylor College of Dentistry, Texas A&M University System Health Science Center, Dallas, Texas, USA.
Guo
Feng-Jin
FJ
Jiang
Bai-Chun
BC
Zhang
Yan
Y
Frenkel
Sally
S
Wang
Da-Wei
DW
Tang
Wei
W
Xie
Yixia
Y
Liu
Chuan-Ju
CJ
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
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