Bone morphogenetic protein-2-derived osteogenic peptide promotes bone regeneration via osteoblastogenesis

Introduction: Bone morphogenetic protein (BMP)-2 plays a critical role in stimulating human mesenchymal stromal cells (hMSCs) differentiation, a key process in bone regeneration. However, the clinical application of BMP-2 has been hindered by several adverse effects. This study evaluated the effectiveness of a newly synthesized BMP2-derived osteogenic peptide (OP), which may overcome the limitations of BMP-2 while preserving its osteogenic potential. Methods: OP5, selected from the OP family based on its osteogenic potential, was tested in vitro to compare its effects on osteogenic signaling, osteoblast differentiation, and hMSC gene expression in with those of BMP-2. New bone formation stimulated by OP5 or BMP-2 was assessed in vivo using radiographic and histological analyses in a rat model of calvarial defects. Results: The optimal OP5 concentration of 1 μM supported hMSC viability and exhibited potent osteogenic activity. OP5 significantly activated BMP receptor types IA and II binding and the osteogenic protein kinase A and phosphorylated cAMP response element-binding protein signaling pathway. OP5-induced gene expressions of alkaline phosphatase and osteocalcin peaked on day 4 (early osteogenesis) and were sustained until day 14 (late osteogenesis). In vivo, 100 μg OP5 demonstrated superior bone formation compared to other doses (50, 300, and 600 μg), but was less effective than BMP-2. The amount of bone regeneration varied with different doses of OP5. Conclusions: OP5, a low-molecular-weight peptide with strong osteogenic potential, may be a viable alternative to BMP-2 for clinical bone regeneration, minimizing BMP2-associated adverse effects.