Effect of BMP-2 Derived Peptide Grafted to Nanoparticles on Differentiation of Stromal Cells
- PDF / 818,856 Bytes
- 6 Pages / 612 x 792 pts (letter) Page_size
- 65 Downloads / 164 Views
Effect of BMP-2 Derived Peptide Grafted to Nanoparticles on Differentiation of Stromal Cells Esmaiel Jabbari, Angel E. Mercado, Junyu Ma, and Xuezhong He Biomimetic Materials and Tissue Engineering Laboratory, University of South Carolina Columbia, SC 29208, U.S.A.
ABSTRACT Recombinant human bone morphogenetic protein (rhBMP-2) plays a major role in differentiation of marrow stromal cells (MSCs). Peptides based on the active domains of rhBMP2, like the LYLTSIASLETPVSSAKPIK (BMP peptide), have been proposed as an alternative to reduce the side effects associated with high doses of rhBMP-2. The objective of this work was to determine the osteogenic activity of the BMP peptide grafted to poly(lactide fumarate) nanoparticles (PLAF NPs). A cysteine-terminated BMP peptide was grafted to PLAF NPs by linking the cysteine residue to the fumarate groups. Groups included blank NPs, free BMP peptide, free BMP-2 protein, and BMP-grafted NPs. The decrease in cell numbers after 21 days was consistent with an increase in mineral content and decrease in proliferation with osteogenic differentiation of MSCs. Alkaline phosphatase (ALPase) activity peaked at 14 days, consistent with the start of the osteogenic cascade. A slightly higher mineral content was observed in the BMP-grafted NP group after 14 days. m-RNA and immunostaining showed that cells in the BMP-grafted NP group had a higher content of osteocalcin protein after 21 days. Results suggest that the BMP-grafted NPs have a greater affinity to BMP cell surface receptors, leading to a stronger activation of the pathways leading to osteogenesis.
INTRODUCTION rhBMP-2 plays a major role in initiating the cascade of chemotaxis, differentiation of MSCs and bone regeneration [1]. High doses coupled with the diffusion of rhBMP-2 away from the intended site of regeneration cause adverse effects such as bone overgrowth, immunological reaction, and tumorigenesis [2]. An attractive alternative to rhBMP-2 protein therapy is to use peptides, based on the active domains of rhBMP-2, to initiate the cascade of osteogenesis. For example, the peptide LYLTSIASLETPVSSAKPIK (hereafter designated as BMP peptide), corresponding to residues 73-92 of the knuckle epitope of rhBMP-2 has significantly higher alkaline phosphatase (ALPase) activity than sequences 68-87, 68-92, 78-97, and 44-58, and inhibits rhBMP-2 binding to both type I and type II BMP receptors [3]. It is hypothesized that the BMP peptide grafted to resorbable nanoparticles (NPs) provides a multivalent form of the peptide for stronger interaction with cell surface receptors and higher expression of osteogenic markers, leading to accelerated bone formation and potentially reducing the side effects observed with the whole rhBMP-2 protein.
The objective of this work was to investigate the release characteristics and osteogenic activity of BMP peptide grafted to self-assembled biodegradable NPs. In this work, cysteineterminated BMP peptide is grafted to poly(lactide fumarate)/poly(lactide-co-ethylene oxide fumarate) (PLAF/PLEOF) self-a
Data Loading...
