Periostin promotes ectopic osteogenesis of CTLA4-modified bone marrow mesenchymal stem cells

Abstract

The improved ectopic osteogenesis of cytotoxic T-lymphocyte–associated antigen 4-Ig-modified bone marrow mesenchymal stem cells (MSCs-CTLA4) has been demonstrated but the mechanisms involved remain to be determined. The extracellular matrix (ECM) has recently been reported to play a vital role in bone formation and periostin (POSTN) has been suggested as a key member in constructing the ECM in bone tissue. We found that POSTN expression in the MSCs-CTLA4 group is significantly enhanced compared with that in the MSCs group, not only in tissue-engineered bone (TEB) with femur heterotopic transplantation in vivo but also under the immune activation condition in vitro. This ectopic osteogenesis effect is in accordance with POSTN expression. We also found that the soluble POSTN treatment up-regulates osteogenic marker expression in MSCs, including runt-related transcription factor 2, collagen 1, osteocalcin, osterix, and alkaline phosphatase and calcium nodule formation. These effects are diminished when the soluble POSTN is neutralized. Our results demonstrate that POSTN promotes the osteogenic differentiation of MSCs and that CTLA4 enhances the ectopic osteogenesis of MSCs-CTLA4-based TEB, potentially by maintaining POSTN expression in xenotransplantation.