Meniscal repair possibilities using bone morphogenetic protein-7

Abstract

This study analysed the influence of bone morphogenetic protein-7 (BMP-7) on cells and meniscal structure. The effect of treatment with BMP-7 was assessed in vitro and in vivo in lesions in the avascular area of the meniscus. Cells were extracted from the outer and inner part of eight menisci of four 2-year-old merino sheep. The menisci were digested with a collagenase mix, and meniscus cells of the synovium, vascular area and avascular area were extracted. The expression of genes for collagen (Col1 and Col2A), matrix metalloproteinases (MMP-2 and MMP-13) and aggrecan was analysed by real time quantitative polymerase chain reaction (qPCR) at baseline and after incubation with BMP-7. Eight sheep aged 2 years and weighing 35-40 kg were used for the in vivo study. Surgery was performed in both knees of every animal. Two holes were made in the avascular area of the medial meniscus of both knees and filled using Putty(®) (control groups) or OP-1 Putty(®), which comprises BMP-7 mixed with a cellulose putty carrier (experimental groups). Animals were sacrificed at 6, 12 and 25 weeks. Adding BMP-7 to vascular cells of the meniscus was associated with a 15-fold increase in Col2A expression and a 78-fold increase in BMP-7 expression. BMP-7 inhibited MMP-2 and MMP-13 expression. Adding BMP-7 to synovial cells inhibited the expression of Col1, doubled the expression of Col2A and reduced the expression of BMP-7; the expression of MMP-2 was inhibited, while that of MMP-13 was increased three-fold. Incubation of cells from the avascular region with BMP-7 was associated with a 2.4-fold increase in Col1 expression, and a 4.4-fold increase in Col2A expression compared with the control. The expression of MMP-2 and BMP-7 was inhibited. In the in vivo study, treatment of the holes in the avascular area of the meniscus with BMP-7 was associated with an important cell presence inside the holes and the appearance of fibrous tissue after 12 weeks; these features were not seen in the control groups. BMP-7 may be a suitable growth factor for stimulation of meniscal cell and collagen formation.