TY  - JOUR
A1  - Xu, Jietao
A1  - Fahmy-Garcia, Shorouk
A1  - Wesdorp, Marinus A.
A1  - Kops, Nicole
A1  - Forte, Lucia
A1  - De Luca, Claudio
A1  - Misciagna, Massimiliano Maraglino
A1  - Dolcini, Laura
A1  - Filardo, Giuseppe
A1  - Labberté, Margot
A1  - Vancíková, Karin
A1  - Kok, Joeri
A1  - van Rietbergen, Bert
A1  - Nickel, Joachim
A1  - Farrell, Eric
A1  - Brama, Pieter A. J.
A1  - van Osch, Gerjo J. V. M.
T1  - Effectiveness of BMP-2 and PDGF-BB adsorption onto a collagen/collagen-magnesium-hydroxyapatite scaffold in weight-bearing and non-weight-bearing osteochondral defect bone repair: in vitro, ex vivo and in vivo evaluation
JF  - Journal of Functional Biomaterials
N2  - Despite promising clinical results in osteochondral defect repair, a recently developed bi-layered collagen/collagen-magnesium-hydroxyapatite scaffold has demonstrated less optimal subchondral bone repair. This study aimed to improve the bone repair potential of this scaffold by adsorbing bone morphogenetic protein 2 (BMP-2) and/or platelet-derived growth factor-BB (PDGF-BB) onto said scaffold. The in vitro release kinetics of BMP-2/PDGF-BB demonstrated that PDGF-BB was burst released from the collagen-only layer, whereas BMP-2 was largely retained in both layers. Cell ingrowth was enhanced by BMP-2/PDFG-BB in a bovine osteochondral defect ex vivo model. In an in vivo semi-orthotopic athymic mouse model, adding BMP-2 or PDGF-BB increased tissue repair after four weeks. After eight weeks, most defects were filled with bone tissue. To further investigate the promising effect of BMP-2, a caprine bilateral stifle osteochondral defect model was used where defects were created in weight-bearing femoral condyle and non-weight-bearing trochlear groove locations. After six months, the adsorption of BMP-2 resulted in significantly less bone repair compared with scaffold-only in the femoral condyle defects and a trend to more bone repair in the trochlear groove. Overall, the adsorption of BMP-2 onto a Col/Col-Mg-HAp scaffold reduced bone formation in weight-bearing osteochondral defects, but not in non-weight-bearing osteochondral defects.
KW  - tissue engineering
KW  - regenerative medicine
KW  - osteochondral lesion
KW  - biocompatible materials
KW  - bone morphogenetic proteins
KW  - platelet-derived growth factor
KW  - animal model
KW  - weight-bearing
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304019
SN  - 2079-4983
VL  - 14
IS  - 2
ER  - 
TY  - JOUR
A1  - Mueller, Thomas D.
A1  - Fiebig, Juliane E.
A1  - Weidauer, Stella E.
A1  - Qiu, Li-Yan
A1  - Bauer, Markus
A1  - Schmieder, Peter
A1  - Beerbaum, Monika
A1  - Zhang, Jin-Li
A1  - Oschkinat, Hartmut
A1  - Sebald, Walter
T1  - The Clip-Segment of the von Willebrand Domain 1 of the BMP Modulator Protein Crossveinless 2 Is Preformed
JF  - Molecules
N2  - Bone Morphogenetic Proteins (BMPs) are secreted protein hormones that act as morphogens and exert essential roles during embryonic development of tissues and organs. Signaling by BMPs occurs via hetero-oligomerization of two types of serine/threonine kinase transmembrane receptors. Due to the small number of available receptors for a large number of BMP ligands ligand-receptor promiscuity presents an evident problem requiring additional regulatory mechanisms for ligand-specific signaling. Such additional regulation is achieved through a plethora of extracellular antagonists, among them members of the Chordin superfamily, that modulate BMP signaling activity by binding. The key-element in Chordin-related antagonists for interacting with BMPs is the von Willebrand type C (VWC) module, which is a small domain of about 50 to 60 residues occurring in many different proteins. Although a structure of the VWC domain of the Chordin-member Crossveinless 2 (CV2) bound to BMP-2 has been determined by X-ray crystallography, the molecular mechanism by which the VWC domain binds BMPs has remained unclear. Here we present the NMR structure of the Danio rerio CV2 VWC1 domain in its unbound state showing that the key features for high affinity binding to BMP-2 is a pre-oriented peptide loop.
KW  - bone morphogenetic proteins
KW  - TGF-β superfamily
KW  - BMP antagonist
KW  - protein-protein recognition
KW  - NMR spectroscopy
KW  - von Willebrand type C domain
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97196
ER  - 
TY  - JOUR
A1  - Kübler, N.
A1  - Reuther, J.
A1  - Kirchner, T.
A1  - Pfaff, M.
A1  - Müller-Hermelink, H. K.
A1  - Albert, R.
A1  - Sebald, Walter
T1  - IgG monoclonal antibodies that inhibit osteoinductivity of human bone matrix-derived proteins (hBMP/NCP)
N2  - Monoclonal hBMP/NCP (human bone morphogenetic protein anrl associaterl noncollagenous proteins) antiborlies of the lgG class were prorlucerl. In vitro, 12 of 19 hBMP/NCP antiborlies showerl functional inhibition of hBMP/ NCP-induced chondroneogenesis in a neonatal muscle tissue assay. Inducing factors were characterized by their inhibiting antibodies with immunoblotting. Several peptide factors seem to be involved in the cascade of inducerl chondro- and osteogenesis.
KW  - Biochemie
KW  - bone morphogenetic proteins
KW  - neutralizing antibodies
KW  - cartilage induction
Y1  - 1994
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62388
ER  -