Osteogenic Growth Peptide, OGP

Role of Osteogenic Growth Peptide (OGP) and OGP(10-14) in Bone Regeneration: A Review

Bone regeneration is a process that involves several molecular mediators, such as growth factors, which directly affect the proliferation, migration and differentiation of bone-related cells. The osteogenic growth peptide (OGP) and its C-terminal pentapeptide OGP(10-14) have been shown to stimulate the proliferation, differentiation, alkaline phosphatase activity and matrix mineralization of osteoblastic lineage cells. However, the exact molecular mechanisms that promote osteoblastic proliferation and differentiation are not completely understood. This review presents the main chemical characteristics of OGP and/or OGP(10-14), and also discusses the potential molecular pathways induced by these growth factors to promote proliferation and differentiation of osteoblasts. Furthermore, since these peptides have been extensively investigated for bone tissue engineering, the clinical applications of these peptides for bone regeneration are discussed.

Osteogenic growth peptide (OGP)-loaded amphiphilic peptide (NapFFY) supramolecular hydrogel promotes osteogenesis and bone tissue reconstruction

Efficient bone reconstruction after bone injury remains a great challenge. Injectable supramolecular hydrogels based on amphiphilic peptide have been widely used due to their good biocompatability, non-immunogenicity, and manipulable physicochemical properties by sequence design. Herein, we used a well-studied hydrogelator, NapFFY, to coassemble with osteogenic growth peptide (OGP) to prepare a supramolecular hydrogel, NapFFY-OGP. Both in vitro and in vivo studies demonstrate that OGP was ideally synchronously, and continuously released from the hydrogel to effectively promote the regeneration and reconstruction of skull bone defects. More specifically, after the embedding the rat skull defect area with NapFFY-OGP hydrogels, a bone regeneration rate of 37.54% bone volume fraction (BV/TV) was achieved compared to that of NapFFY hydrogel group (25.09%). NapFFY-OGP hydrogel shows great promise in the clinic repair of bone defects in the future.

Osteogenic growth peptide enhances osteogenic differentiation of human periodontal ligament stem cells

Bone tissue engineering consists of three major components namely cells, scaffolds, and signaling molecules to improve bone regeneration. These integrated principles can be applied in patients suffered from bone resorption diseases, such as osteoporosis and periodontitis. Osteogenic growth peptide (OGP) is a fourteen-amino acid sequence peptide that has the potential to regenerate bone tissues. This study aimed to disseminate the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) with OGP treatment. OGP was elaborated for proliferation, cytotoxicity, osteogenic differentiation effects, and the involvement of osteogenic related signaling pathways in vitro. This study found that OGP at lower concentration shows better effects on cytotoxicity and proliferation. Moreover, OGP at concentration 0.01 nM had the most potential to differentiate hPDLSCs toward osteogenic lineage comparing with higher concentrations of OGP. The phenomenon was mainly involving transforming growth factor-beta (TGF-β), bone morphogenetic protein (BMP), Hedgehog, and Wingless-related (Wnt) pathways. Further, SB-431542 treatment demonstrated the partial involvement of OGP in regulating osteogenic differentiation of hPDLSCs. In conclusion, OGP at low concentration enhances osteogenic differentiation of hPDLSCs by governing TGF-β signaling pathway.

Covalently functionalized poly(etheretherketone) implants with osteogenic growth peptide (OGP) to improve osteogenesis activity

Polyetheretherketone (PEEK), as the most promising implant material for orthopedics and dental applications, has bone-like stiffness, excellent fatigue resistance, X-ray transparency, and near absence of immune toxicity. However, due to biological inertness, its bone conduction and bone ingrowth performance is limited. The surface modification of PEEK is an option to overcome these shortcomings and retain most of its favorable properties, especially when excellent osseointegration is desired. In this study, a simple reaction procedure was employed to bind the osteogenic growth peptide (OGP) on the surface of PEEK materials by covalent chemical grafting to construct a bioactive interface. The PEEK surface was activated by N,N'-disuccinimidyl carbonate (DSC) after hydroxylation, and then OGP was covalently grafted with amino groups. The functionalized surface of PEEK samples were characterized by X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FT-IR), water contact angle measurement and biological evaluation in vitro. OGP-functionalized PEEK surface significantly promoted the attachment, proliferation, alkaline phosphatase (ALP) activity and mineralization of pre-osteoblast cells (MC3T3-E1). The in vivo rat tibia implantation model is adopted and micro-CT analyses demonstrated that the OGP coating significantly promoted new bone formation around the samples. The in vitro and in vivo results reveal that the modification by covalent chemical functionalization with OGP on PEEK surface can augment new bone formation surrounding implants compared to bare PEEK and PEEK implant modified by covalently attached OGP is promising in orthopedic and dental applications.

Mitogenic action of osteogenic growth peptide (OGP): role of amino and carboxy-terminal regions and charge

We have recently reported the discovery of a 14-amino-acid osteogenic growth peptide (OGP). In vivo OGP increases bone formation and trabecular bone density. Physiologically it is found in serum complexed to an OGP binding protein (OGPBP). In vitro OGP has a biphasic effect on osteoblastic MC 3T3 E1 and fibroblastic NIH 3T3 cell proliferation; at low concentrations (0.01-1.0 and 1.0-100.0 pM, respectively) it is highly stimulatory with an inhibition at higher doses. To assess possibilities of labeling synthetic OGP to obtain radio- or fluorescent ligands, OGP analogues were extended at the N- or C-termini with Cys or Cys(S-NEtSucc) or the OGP Tyr-10 replaced by 3-I(Tyr). All analogues with N-terminal modifications, as well as the [Cys15]OGP-NH2 retained the OGP-like dose-dependent effect on proliferation of the MC 3T3 E1 and NIH 3T3 cells, although the magnitude of stimulation was lower, approx. 2/3 that of the native-like synthetic OGP. The [Cys15(S-NEtSucc)]OGP-NH2 and [3-I(Tyr10)]OGP shared only the inhibitory activity of OGP. This suppression is further shared by a number of other positively and negatively net charged, but not net neutral, peptides. Both N-terminal-modified analogues displayed a decreased binding activity to the OGPBP. All analogues except reverse OGP, [3-I(Tyr10)]OGP and [Cys15(S-NEtSucc)]OGP-NH2 reacted with anti-OGP antibodies. These data are not only important for labeling purposes but suggest a respective role for the OGP N-and C-terminal regions in binding to the OGPBP and putative OGP receptor. It appears that the OGP proliferative activity represents the net effect of stimulation specific to the OGP structure and nonspecific inhibition associated with the peptide's high positive net charge.