Swelling and inflammation after rhBMP-2 use are dose-dependent. Swelling may be due to direct contact as well as spread in the plane of access. The causes are a robust inflammatory reaction as well as sterile seroma and encapsulated hematoma formation.

HATDMSCs transfected with adeno-BMP-2 induce abundant bone formation and have a similar posterolateral spinal fusion in rats as similarly genetically modified HBMDMSCs. Both are potential strategies for spinal fusion and may be a more efficient method of obtaining spinal fusion over currently used grafting substances.

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BMP-2-producing RBMCs developed using lentiviral gene transfer induced more abundant bone within the fusion mass than the RBMCs transduced via adenoviral gene transfer and recombinant protein therapy.

Secreted phosphoprotein 24 kDa (spp24) is a bone matrix protein. It contains a TGF-b receptor II homology 1 (TRH1) domain. A cyclic, synthetic 19 amino acid peptide (bone morphogenetic protein binding peptide or BBP) based on the sequence of the TRH1 domain enhances BMP-2 induced osteogenesis. Many observations suggest that different size forms of this protein have very different effects (inhibiting or enhancing) on BMP-2 induced osteogenesis. Using the stable recombinant Met(His) 6 -tagged secretory form of full-length (fl) bovine spp24 [Met(His) 6 -spp24 (residues 24-203)] and transgenic (TG) mice expressing fl bovine spp24 (residues 1-203), we have demonstrated that spp24 inhibits BMP-2 induced bone formation. The effects of Met(His) 6 -spp24 (24-203) were determined in the ectopic bone-forming bioassay in male mice. Implantation of 5 mg of BMP-2 stimulated bone formation, assessed densitometrically as bone area and mineral content. When Met(His) 6 -spp24 (24-203) was implanted with BMP-2, it elicited a dose-dependent decrease in BMP-2-medicated ectopic bone formation. When added at a 50-fold excess (w/w), Met(His) 6 -spp24 (24-203) completely ablated the effects of BMP-2, while addition of a 10-fold excess had no effect. Constitutive expression of fl bovine spp24 (1-203) under the control of the osteocalcin promoter in TG female mice reduced femoral and vertebral bone mineral density at 3 months of age and reduced femoral BMD at 8 months of age, but had no effects in male mice, which can exhibit less osteocalcin-promoter driven gene transcription than females. Histomorphometric analysis demonstrated that bone volume and trabecular thickness were lower in TG female mice at 3 months of age than in sex-and age-matched wild type (WT) controls. Thus, fl spp24 and its secretory isoform (Met(His) 6 -spp24 ), which contain a BMP-binding or TRH1 motif, inhibit ectopic bone formation in male mice and adversely affects BMD and histological parameters related to bone mass and formation in female mice expressing the human transgene. Under these conditions, fl spp24 acts as a BMP antagonist in vivo. Keywords: bone formation; spp24; bone morphogenetic protein Secreted phosphoprotein-24 (spp24) is a 24 kDa protein of unknown function first cloned from bovine bone matrix.1 The calculated molecular weight of the fulllength unprocessed precursor [bovine spp24 (residues 1-203)] is 23.1 kDa (Swiss-Prot database; AC #Q27967). The first 23 amino acid residues of bovine spp24 (1-203) constitute a signal peptide that is cleaved when the protein is secreted in its mature form [spp24 (24-203)]. The protein contains two internal disulfide bonds linking residues 86 to 97 and 110 to 128, respectively, and contains internal domains with sequence homology to cystatins (cysteine protease inhibitors) and cathelicidins (protease-sensitive precursors of endogenous antibiotic peptides).1 Recent work demonstrated that an 18.5 kDa protein in the osteogenic fraction that Urist et al.2 isolated from demineralized bone matrix (DBM) by hy...