Periostin promotes ectopic osteogenesis of CTLA4-modified bone marrow mesenchymal stem cells
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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.
KeywordsBone marrow mesenchymal stem cells Tissue-engineered bone Extracellular matrix Osteogenic differentiation Immunosuppression
The authors declare that they have no conflict of interest. This study was funded by the National Natural Science Foundation of China (grant number: 81601627, 31170931). The manuscript was edited and proofread by Medjaden Bioscience.
- Horiuchi K, Amizuka N, Takeshita S, Takamatsu H, Katsuura M, Ozawa H, Toyama Y, Bonewald LF, Kudo A (1999) Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta. J Bone Miner Res 14:1239–1249CrossRefPubMedGoogle Scholar
- Norris RA, Damon B, Mironov V, Kasyanov V, Ramamurthi A, Moreno-Rodriguez R, Trusk T, Potts JD, Goodwin RL, Davis J, Hoffman S, Wen X, Sugi Y, Kern CB, Mjaatvedt CH, Turner DK, Oka T, Conway SJ, Molkentin JD, Forgacs G, Markwald RR (2007) Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues. J Cell Biochem 101:695–711CrossRefPubMedPubMedCentralGoogle Scholar
- Rios H, Koushik SV, Wang H, Wang J, Zhou HM, Lindsley A, Rogers R, Chen Z, Maeda M, Kruzynska-Frejtag A, Feng JQ, Conway SJ (2005) Periostin null mice exhibit dwarfism, incisor enamel defects, and an early-onset periodontal disease-like phenotype. Mol Cell Biol 25:11131–11144CrossRefPubMedPubMedCentralGoogle Scholar