Defective endochondral ossification in mice with strongly compromised expression of JunB.
Functional analysis in mice has established an absolute requirement of JunB, a member of the AP-1 transcription factor family, during early embryonic development. To investigate the role of JunB during mid and late gestation and postnatally Ubi-junB transgenic mice were used to generate two junB-/- Ubi-junB mutant lines, in which embryonic lethality was rescued but strongly reduced JunB expression in several adult tissues was observed. Mutant mice from both rescue lines were growth retarded and shared significantly reduced longitudinal bone growth. Mutant long bones were characterised by reduced numbers of growth plate chondrocytes and a severe osteoporosis. Decreased JunB levels in epiphysal growth plate chondrocytes and bone lining osteoblasts correlated with deregulated expression of Cyclin A, Cyclin D1 and p16INK4a, key regulators of cell cycle control. Furthermore, junB-/- Ubi-junB bone marrow stromal cells were unable to differentiate into bone forming osteoblasts in vitro. Our data demonstrate that JunB plays a crucial role in endochondral ossification by regulating proliferation and function of chondrocytes and osteoblasts.
Hess
Jochen
J
Deutsches Krebsforschungszentrum Heidelberg (DKFZ), Division of Signal Transduction and Growth Control (A100), Im Neuenheimer Feld 280, D-69120 Heidelberg.
Hartenstein
Bettina
B
Teurich
Sibylle
S
Schmidt
Dirk
D
Schorpp-Kistner
Marina
M
Angel
Peter
P
D000818:Animals; D001846:Bone Development / Q000235:genetics / Q000502:physiology*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010024:Osteoporosis / Q000378:metabolism* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019925:Cyclin A; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016755:Proto-Oncogene Proteins c-jun; D019938:Cyclin D1