Affiliations: "Signaling and Gene Regulation", Gesellschaft für
Biotechnologische Forschung (GBF), Braunschweig, Germany | Skeletal Biotechnology Laboratory, Hebrew
University-Hadassah Medical Center, Jerusalem, Israel | Rheumatologie, Charité, Berlin, Germany
Note: [] Address for correspondence: G. Gross, Gesellschaft für
Biotechnologische Forschung (GBF), Mascheroder Weg 1, 38124 Braunschweig,
Germany. Tel.: +49 531 6181 212; Fax: +49 531 6181 202; E-mail: [email protected]
Abstract: 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.
