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Control of the bone morphogenetic protein 7 gene in developmental and adult life.

ABSTRACT: The TGFbeta superfamily growth factor BMP7 performs essential biological functions in embryonic development and regeneration of injured tissue in the adult. BMP7 activity is regulated at numerous levels in the signaling pathway by the expression of extracellular antagonists, decoy receptors and inhibitory cell signaling components. Additionally, expression of the BMP7 gene is tightly controlled both during embryonic development and adult life. In this review, the current status of work on regulation of BMP7 at the genomic level is discussed. In situ hybridization and reporter gene studies have conclusively defined patterns of BMP7 expression in many tissues. Additionally, both in vivo and cell culture studies have defined some of the mechanistic bases for this regulation. In addition to transcriptional activation mediated by binding of activating transcription factors, there is also strong evidence for repression through recruitment of histone modifying enzymes to specific genetic elements. This review summarizes our current understanding of BMP7 gene regulation in embryonic development and adult tissues.

SUBMITTER: Oxburgh L

PROVIDER: S-EPMC2709933 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Control of the bone morphogenetic protein 7 gene in developmental and adult life.

Oxburgh Leif L

Current genomics 20090601 4

The TGFbeta superfamily growth factor BMP7 performs essential biological functions in embryonic development and regeneration of injured tissue in the adult. BMP7 activity is regulated at numerous levels in the signaling pathway by the expression of extracellular antagonists, decoy receptors and inhibitory cell signaling components. Additionally, expression of the BMP7 gene is tightly controlled both during embryonic development and adult life. In this review, the current status of work on regula ...[more]

PMID: 19949543

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Project description:The repair and treatment of lost or damaged alveolar bone is of great significance in dentistry. Gene-activated matrix (GAM) technology provides a new way for bone regeneration. It is a local gene delivery system, which can not only recruit cells, but also influence their fate. For this purpose, we fabricated a bone morphogenetic protein 2 (BMP-2) gene-loaded absorbable gelatin sponge (AGS) and studied its effect on promoting alveolar bone formation and preventing resorption following tooth extraction in rats. In order to obtain better transfection efficiency, polyethylenimine-alginate (PEI-al) nanocomposites were synthesized and used as gene vectors to deliver BMP-2 cDNA plasmids (PEI-al/pBMP-2). The transfection efficiency, BMP-2 protein expression and osteogenic differentiation of the cells were investigated in vitro. In vivo, we established an alveolar bone regeneration model by extracting the rats' left mandibular incisors. The rats were randomly assigned into 3 groups: control group, unfilled sockets; AGS group, sockets filled with PEI-al solution-loaded gelatin sponges; AGS/BMP group, sockets filled with PEI-al/pBMP-2 solution-loaded gelatin sponge. Radiological and histological assays were performed at 4 and 8 weeks later. In vitro transfection assays indicated that PEI-al/pBMP-2 complexes could effectively transfect MC3T3-E1 cells, promoting the secretion of BMP-2 protein for at least 14 days, as well as increasing the expression of osteogenesis-related gene, ALP activity and calcium deposition. In vivo, western blot analysis showed BMP-2 protein was expressed in bone tissues of AGS/BMP group. The relative height of the residual alveolar ridge and bone mineral density (BMD) of the AGS/BMP group were significantly greater than those in the AGS and control groups at 4 and 8 weeks, respectively. Histological examination showed that, at 4 weeks, osteoblasts had grown in a cubic shape around the new bone in the AGS/BMP group, suggesting new bone formation. In conclusion, the combination of PEI-al/pBMP-2 complexes and gelatin sponge could promote alveolar bone regeneration, which may provide an easy and valuable method for alveolar ridge preservation and augmentation.

Dataset Information

Control of the bone morphogenetic protein 7 gene in developmental and adult life.

Publications

Control of the bone morphogenetic protein 7 gene in developmental and adult life.

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