Abstract
Based on previous gene therapy studies in bone formation induced by BMP adenoviral vectors, the osteogenic potentials of different BMP adenoviral vectors (ADhBMP-2, -4, -6, -7, and -9) are very high in immunodeficient animals but vary significantly among immunocompetent animals. We have demonstrated that the amounts of bone formation in immunocompetent animals were not significantly affected by use of different generations of adenoviral vectors and different species of BMPs. The similar protein expression curves between immunodeficient and immunocompetent rats indicated that reduced amount of BMP expression was not the main factor limiting the bone formation. Nevertheless, some components of sera may specifically block the signal transduction pathways of particular BMPs, thus interrupting bone formation. We use the term |[ldquo]|bone formation inhibitors (BFIs)|[rdquo]| to describe these immune factors to distinguish them from |[ldquo]|BMP antagonists|[rdquo]|, which are mainly secreted by bone tissue. A mouse skeletal muscle myoblast cell line (C2C12) was used as a model. Reduction of alkaline phosphatase (AP) expression was used as an index to evaluate the inhibiting activity of serum. The distribution of BFIs among different animal species and strains was investigated. Sera from rabbit, rat, and mice were tested. Sera from two strains of rabbit included 14 normal control sera and five adenovirus-vaccinated sera. Most rabbit sera did not exhibit significant inhibiting activity on cell response to any BMP. Only one serum from adenovirus-vaccinated rabbit displayed inhibiting activity on cell response to BMP6. Two sera from NOD SCID mice did not show any inhibiting activity on cell response to BMP2, -6 and -9. Forty-four sera obtained from athymic nude, SD, and Wistar rats were tested. From athymic nude rats we obtained five normal and seven adenovirus-vaccinated sera. All the rat sera inhibited response of cells to BMP6. Two sera obtained from adenovirus (ADLUC)-vaccinated athymic nude rats 16 months after the vaccination inhibited cell response to BMP2, -6, and -9. Four sera from untreated Wistar rats demonstrated inhibiting activities to all three BMPs. Sera from 13 normal, and 15 adenovirus-vaccinated SD rats, all displayed inhibiting activity to BMP6. Some sera also showed inhibition of cell response to BMP2 and -9. The results indicate that BFIs are widely distributed among different animal species and strains. Adenovirus-vaccinated sera may have higher titers than normal sera. This finding will provide a new point of view to assess the relationship between the immune system and BMPs.
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