title: The influence of the stable expression of BMP2 in fibrin clots on the remodelling and repair of osteochondral defects.
abstract: 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.
authors.affiliation: Department of Orthopaedics and Traumatology, TU Munchen, Ismaninger Str. 22, 81675 Munich, Germany. stephan-vogt@web.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Vogt
authors.forename: Gabriele
authors.initials: G
authors.lastname: Wexel
authors.forename: Thomas
authors.initials: T
authors.lastname: Tischer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schillinger
authors.forename: Peter
authors.initials: P
authors.lastname: Ueblacker
authors.forename: Bettina
authors.initials: B
authors.lastname: Wagner
authors.forename: Daniel
authors.initials: D
authors.lastname: Hensler
authors.forename: Jonas
authors.initials: J
authors.lastname: Wilisch
authors.forename: Christopher
authors.initials: C
authors.lastname: Geis
authors.forename: Daniela
authors.initials: D
authors.lastname: Wübbenhorst
authors.forename: Joachim
authors.initials: J
authors.lastname: Aigner
authors.forename: Michael
authors.initials: M
authors.lastname: Gerg
authors.forename: Achim
authors.initials: A
authors.lastname: Krüger
authors.forename: Gian M
authors.initials: GM
authors.lastname: Salzmann
authors.forename: Vladimir
authors.initials: V
authors.lastname: Martinek
authors.forename: Martina
authors.initials: M
authors.lastname: Anton
authors.forename: Christian
authors.initials: C
authors.lastname: Plank
authors.forename: Andreas B
authors.initials: AB
authors.lastname: Imhoff
authors.forename: Bernd
authors.initials: B
authors.lastname: Gansbacher
mesh_terms: 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*
chemical_list: D055396:Bone Morphogenetic Protein 2; D005337:Fibrin; D000469:Alkaline Phosphatase