Thurs., 10/14/10 Basic Science, Paper #37, 4:40 pm OTA-2010
Comparison of Osteogenic Potential of Different Bone Morphogenetic Proteins
Jessica D. Cross, MD1,2; Christopher R. Rathbone, PhD2; Joseph C. Wenke, PhD2;
1United State Army Institute of Surgical Research and Brooke Army Medical Center,
San Antonio, Texas, USA;
2United States Army Institute of Surgical Research, Fort Sam Houston, Texas, USA
Purpose: This investigation was conducted to compare the osteogenic potential of the bone morphogenetic proteins (BMPs) 2, 4, 5, 6, 7, and 9 in multiple cell types.
Methods: C3H10T1/2, C2C12, human bone marrow–derived stem cells, and human adipose– derived stem cells were seeded on 24-well plates. BMP-2, 4, 5, 6, 7, and 9 were added at 10, 50, 100, 250, and 500 ng/mL for 3 days. Cell lysates were obtained at 3 and 7 days after BMP treatment for the determination of alkaline phosphatase activity.
Results: In both immortalized cell lines, the C3H10T1/2 cells and C2C12 cells, BMP-9 resulted in statistically significant higher alkaline phosphatase levels at day 3 compared to the other BMPs (P < 0.05). In the bone marrow–derived cells, alkaline phosphatase activity was modest; however, BMP-9 at all doses greater than 50 ng/mL tended to result in higher activity. In the adipose-derived stem cells, alkaline phosphate activity was quite robust, and the BMP-9–treated cells demonstrated the highest activity compared to the other BMPs (P < 0.001) at all doses greater than 100 ng/mL by day 3. At day 7, both BMP-9 and BMP-6 demonstrated the highest alkaline phosphatase activities compared to the other BMPs at all doses greater than 10 ng/mL (P < 0.001) with little difference between them. Activity due to BMP-2 and BMP-7 treatment was similar. BMPs 4 and 5 consistently resulted in the lowest alkaline phosphatase activity (data not shown in graph).
Conclusions: BMP-9 may possess greater osteogenic potential than the currently US Food and Drug Administration (FDA)-approved BMPs. In general, it stimulated the largest increase in alkaline phosphatase activity, and did so at lower doses. BMP-6 also resulted in high alkaline phosphate activity in some cell lines. Between the two commercially available BMPs, BMP-2 and -7, there was no difference in resultant alkaline phosphatase activity.
Alphabetical Disclosure Listing (292K PDF)
• The FDA has not cleared this drug and/or medical device for the use described in this presentation (i.e., the drug or medical device is being discussed for an “off label” use). ◆FDA information not available at time of printing. Δ OTA Grant.