The influence of the stable expression of BMP2 in fibrin clots on the remodelling and repair of osteochondral defects.
Growth factors like BMP2 have been tested for osteochondral repair, but transfer methods used until now were insufficient. Therefore, the aim of this study was to analyse if stable BMP2 expression after retroviral vector (Bullet) transduction is able to regenerate osteochondral defects in rabbits. Fibrin clots colonized by control or BMP2-transduced chondrocytes were generated for in vitro experiments and implantation into standardized corresponding osteochondral defects (n=32) in the rabbit trochlea. After 4 and 12 weeks repair tissue was analysed by histology (HE, alcian-blue, toluidine-blue), immunohistochemistry (Col1, Col2, aggrecan, aggrecan-link protein), ELISA (BMP2), and quantitative RT-PCR (BMP2, Col1, Col2, Col10, Cbfa1, Sox9). In vitro clots were also analysed by BMP2-ELISA, histology (alcian-blue), quantitative RT-PCR and in addition by electron microscopy. BMP2 increased Col2 expression, proteoglycan production and cell size in vitro. BMP2 transduction by Bullet was efficient and gene expression was stable in vivo over at least 12 weeks. Proteoglycan content and ICRS-score of repair tissue were improved by BMP2 after 4 and 12 weeks and Col2 expression after 4 weeks compared to controls. However, in spite of stable BMP2 expression, a complete repair of osteochondral defects could not be demonstrated. Therefore, BMP2 is not suitable to regenerate osteochondral lesions completely.
Vogt
Stephan
S
Department of Orthopaedics and Traumatology, TU Munchen, Ismaninger Str. 22, 81675 Munich, Germany. stephan-vogt@web.de
Wexel
Gabriele
G
Tischer
Thomas
T
Schillinger
Ulrike
U
Ueblacker
Peter
P
Wagner
Bettina
B
Hensler
Daniel
D
Wilisch
Jonas
J
Geis
Christopher
C
Wübbenhorst
Daniela
D
Aigner
Joachim
J
Gerg
Michael
M
Krüger
Achim
A
Salzmann
Gian M
GM
Martinek
Vladimir
V
Anton
Martina
M
Plank
Christian
C
Imhoff
Andreas B
AB
Gansbacher
Bernd
B
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation; D019736:Prostheses and Implants; D011817:Rabbits; D012038:Regeneration / Q000502:physiology*
D055396:Bone Morphogenetic Protein 2; D005337:Fibrin; D000469:Alkaline Phosphatase