The Factor VII-activating Protease (FSAP) Enhances the Activity of Bone Morphogenetic Protein-2 (BMP-2)

Abstract

Background: Polymorphisms in the gene encoding for Factor VII-activating protease (FSAP) are a risk factor for atherosclerosis and vascular calcification. Results: FSAP mediates proteolytic cleavage and activation of bone morphogenetic protein-2 (BMP-2). Conclusion: FSAP regulates BMP-2-dependent proliferation and osteogenic differentiation of several cell types. Significance: Activation of BMP-2 by FSAP provides a novel mechanistic insight into the actions of FSAP in remodelingassociated diseases.

Activated protein C (APC) can increase bone anabolism via a protease-activated receptor (PAR)1/2 dependent mechanism

“…Another serine protease, factor VII‐activating protease (FSAP) has been recently shown to cleave and enhance the activity of rhBMP‐2. Thus APC may potential have an as yet unrecognized capacity to increase local BMP activity and enhance the effects of exogenously added rhBMPs …”

Factor VII activating protease (FSAP) regulates the expression of inflammatory genes in vascular smooth muscle and endothelial cells

“…Similarly, inhibition of VEGF by FSAP has also been proposed 83 . On the other hand conversion of the zymogen pro-BMP-2 to active BMP-2 increased its activity towards osteoblastic transformation of cells 84 . Another proposed mechanism of cellular activation is through proteolytic cleavage of bFGF.…”

A core domain of the BMP2 proregion is sufficient for the biogenesis of mature homodimeric growth factor

“…SP denotes the signal peptide. In the context of recombinant mammalian expression constructs, the heterologous Ig κ signal peptide, that ensures efficient secretion of the growth factor pro-form, was used (Roedel et al, 2013). Constructs carrying this secretion signal are indicated with an 'r', for example, rpre-pro-BMP2.…”

“…For recombinant expression and secretion of pro-BMP2 in mammalian cell culture, pSecTag2A with an Ig κ signal peptide was used because this signal peptide had been proven to allow efficient secretion of pro-BMP2 (Roedel et al, 2013). To ease reading, secretion constructs with the heterologous signal peptides are indicated with 'r', e.g., rpre-pro-BMP2 or rpre-BMP2, indicating recombinant secretion constructs for the pro-form or mature BMP2, respectively (Figure 3).…”