Distinct roles of BMP receptors Type IA and IB in osteo-/chondrogenic differentiation in mesenchymal progenitors (C3H10T1/2).
The functional roles of BMP type IA and IB receptors mediating differentiation into the osteogenic and chondrogenic lineage were investigated in the mesenchymal progenitor line C3H10T1/2 in vitro. The capacity of type IA and IB BMP receptors was assessed by the forced expression of the wild-type (wtBMPR-IA or IB) and of the kinase-deficient, dominant-negative form (dnBMPR-IA or -IB) in parental C3H10T1/2 progenitors as well as in C3H10T1/2 progenitors which recombinantly express BMP2 (C3H10T1/2-BMP2) or GDF5 (C3H10T1/2-GDF5). Consistent with the higher endogenous expression rate of BMPR-IA in comparison with BMPR-IB, BMPR-IA plays the dominant role in BMP2-mediated osteo-/chondrogenic development. BMPR-IB moderately influences osteogenic and hardly chondrogenic development. BMPR-IB seems to be unable to efficiently activate downstream signaling pathways upon forced expression. However, a mutation conferring constitutive activity to the BMPR-IB receptor indicates that this receptor possesses the capacity to activate downstream signaling cascades. These results suggest that in mesenchymal progenitors C3H10T1/2 BMPR-IA is responsible for the initiation of the osteogenic as well as chondrogenic development and that BMPR-IA and -IB receptor pathways are well separated in this mesenchymal progenitor line and may not substitute each other. In addition this indicates that type IB and IA BMP receptors may transmit different signals during the specification and differentiation of mesenchymal lineages.
Signaling and Gene Regulation, Gesellschaft für Biotechnologische Forschung, Braunschweig, Germany.
Christian
C
Kaps
Andrea
A
Hoffmann
Yoram
Y
Zilberman
Gadi
G
Pelled
Thomas
T
Häupl
Michael
M
Sittinger
Gerd
G
Burmester
Dan
D
Gazit
Gerhard
G
Gross
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019902:Chondrocytes / Q000166:cytology*; D015870:Gene Expression; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D017978:Receptors, Growth Factor / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology
C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C485192:green fluorescent protein, Aequorea victoria; C499469:recombinant human bone morphogenetic protein-2; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; C498211:BMPR1A protein, human; C498214:BMPR1B protein, human; C498212:Bmpr1a protein, mouse; C498215:Bmpr1b protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I