Bone Abstracts

Caspase-7 belongs to executive apoptotic and pro-inflammatory caspases. Recent reports point to novel roles of these caspases, particularly in cell differentiation. As we revealed such function of caspase-7 in odontogenesis, we turned our attention to participation of this molecule in formation of hard tissue in general.

In this work, both type of bones, intramembranous (mandibular/alveolar bone), and endochondral (long bones) were investigated. Mouse heads and front limbs at ED13.5, 14.5, 15.5, 17.5, and P1 and 5 were used for immunohistochemical localisation of activated form of caspase-7 in bone formation.

In both bone types, the activated form of caspase-7 was detected from the beginning of ossification during embryonic development and persisted up to postnatal stages. The activation of caspase-7 positively correlated with osteocalcin, a marker of osteogenesis. The adult bone status was investigated by microCT in the WT vs caspase-7-deficient adult mice. MicroCT revealed differences in both models of ossification. Intramembranous bone in the knock-out mice showed a statistically significant decrease in volume, while the mineral density was not altered. Conversely, endochondral bone showed constant volume but a significant decrease in mineral density in caspase-7 knock-out mice. The trabecular separation and thickness were not altered, however, changes in spatial organization of trabeculae in caspase-7-deficient mice were evident as well as endosteal and periosteal surfaces.

The microCT results confirmed a specific role of caspase-7 in osteogenesis. The different consequence of caspase-7 deficiency in the intramembranous vs endochondral bones corresponds to previously reported specificities in both types of ossification related to the expression patterns of periostin, BMPs or variations in the vascularisation.

Supported by the Grant Agency of the Czech Republic, project P502/12/1285 at the UVPS and P302/12/J059 at the IAPG. The international cooperation runs under GA AV project M200451201.