Use of bone morphogenic protein-7 as a treatment for osteoarthritis - PubMed (original) (raw)

Use of bone morphogenic protein-7 as a treatment for osteoarthritis

Neil Badlani et al. Clin Orthop Relat Res. 2009 Dec.

Abstract

Osteoarthritis is a degenerative disorder resulting from breakdown of articular cartilage. Previous work has shown bone morphogenic protein-7 has a potential protective effect on cartilage during the development of osteoarthritis. The purpose of this study was to determine whether bone morphogenic protein-7 could decrease the amount of cartilage degradation in preexisting osteoarthritis. The rabbit ACLT model was used as a model of osteoarthritis. Bone morphogenic protein-7 was delivered via Alzet osmotic pump to the joint 4 weeks after anterior cruciate ligament transection; thus cartilage injury was preexisting. The experimental group showed less cartilage degradation than the controls, with an average Outerbridge score of 1.9 versus 2.6 for the controls. Histomorphometry showed a trend toward less cartilage degradation in the bone morphogenic protein-7 group when compared with controls. Semiquantitative real-time polymerase chain reaction showed a considerably greater expression of aggrecan in the bone morphogenic protein-7-treated cartilage when compared with controls and less expression of matrix metalloproteinase-3 and matrix metalloproteinase-13, important catabolic mediators. The synovial tissue of the experimental group also showed considerably less expression of matrix metalloproteinase-3, matrix metalloproteinase-13, and aggrecanase. These results indicate bone morphogenic protein-7 may reduce degradation of articular cartilage in osteoarthritis.

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Figures

Fig. 1A–B

Fig. 1A–B

This figure illustrates the calculation of percent deterioration and average defect size. (A) An actual histologic section of cartilage and (B) projection of that section for calculations are shown. (B) The red line represents the ideal cartilage surface, the blue line represents the ideal subchondral plate, and the black line represents the actual cartilage surface. The calculated area between the red and blue lines is the ideal cartilage area, whereas the calculated area between the black and blue lines is the actual cartilage area. One minus the ratio of actual area to ideal area is the percent deterioration. The average defect is calculated as an average amount of depression from the red to black lines.

Fig. 2A–B

Fig. 2A–B

India ink staining of (A) control and (B) BMP-7-treated knees after euthanasia shows more areas of wear and greater depths of fibrillation in the control group.

Fig. 3A–B

Fig. 3A–B

(A) The mean Outerbridge score of the control group (2.6) was higher than the score of the BMP-7-treated group (1.9). (B) The frequency of each Outerbridge score for control and BMP-7 groups shows a far higher percentage of severely worn condyles in the control group.

Fig. 4A–B

Fig. 4A–B

Sample histologic sections of (A) control group condyles and (B) BMP-7-treated condyles, taken perpendicular to the bone in the sagittal plane from the medial femoral condyles, show greater loss of articular cartilage in the control group sections.

Fig. 5A–B

Fig. 5A–B

(A) Histomorphometry data of the percent deterioration of cartilage in the control and BMP-7-treated groups show the percent deterioration of the control group was 30.8% (SD, 8%) of the ideal cartilage surface versus deterioration of only 23.5% (SD, 10%) for the BMP-7-treated condyles (p > 0.05). (B) Histomorphometry data of the average depression or defect of cartilage in the control and BMP-7-treated groups show the average depression of the control group was 0.141 mm (SD, 0.057 mm), whereas the BMP-7-treated group had an average depression of 0.103 mm (SD, 0.062 mm) (p > 0.05).

Fig. 6

Fig. 6

RT-PCR data of the expression of anabolic and catabolic genes in the cartilage tissue of the control and BMP-7-treated groups are shown. The BMP-7-treated cartilage showed an increase in aggrecan expression and decrease (p < 0.05) in MMP-3 and MMP-13 expression when compared with the control group.

Fig. 7

Fig. 7

RT-PCR data of the expression of catabolic genes in the synovial tissue of the control and BMP-7-treated groups show the BMP-7-treated synovium had a decrease (p < 0.05) in aggrecanase, MMP-3, and MMP-13 expression when compared with the control group.

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