Specific amino acids from the broad C-terminal region of BMP-2 are crucial for osteogenesis

Stylianos-Zafeirios Karoulias; Maria Pitou; Rigini Papi; Paraskevas Lamprou; Theodora Choli-Papadopoulou

doi:10.1016/j.bonr.2021.101092

Specific amino acids from the broad C-terminal region of BMP-2 are crucial for osteogenesis

Bone Rep. 2021 May 8:14:101092. doi: 10.1016/j.bonr.2021.101092. eCollection 2021 Jun.

Authors

Stylianos-Zafeirios Karoulias¹, Maria Pitou¹, Rigini Papi¹, Paraskevas Lamprou¹, Theodora Choli-Papadopoulou¹

Affiliation

¹ Laboratory of Biochemistry, School of Chemistry, Faculty of Natural Sciences, Aristotle University of Thessaloniki (AUTh), 54124 Thessaloniki, Greece.

Abstract

The shortest functional domains of growth factor Bone Morphogenetic Protein 2 (BMP-2) that are dynamical implicated in osteogenesis have been investigated and well characterized. In particular, the broad C-terminal region expanding from Val63 to Arg114 as well as its shorter sequence 86-AISMLYLDEN-95 exhibited the highest osteogenic ability for regeneration and reconstruction of bone tissue. In addition, the amino acids Ser88 and Leu90 have been identified as crucial for receptor binding and osteogenic efficacy. Furthermore, the above-mentioned domains in contrary to full length BMP-2 protein signal mainly through the Smad pathway as it is evidenced by phosphorylation decrease of Extracellular-signal-Regulated Kinase (ERK1/2). Taking together, our results are significant for clinical applications regarding the generation of biomaterials and healing of orthopedic fractures.

Keywords: AP, Alkaline Phosphatase; Alizarin Red; Alkaline phosphatase; B2M, beta-2 microglobulin; BMP, Bone Morphogenetic Protein; BMPR, Bone Morphogenetic Protein receptor; ERK, Extracellular signal-Regulated Kinase; MAPK, Mitogen-Activated Protein Kinase; Osteo-implants; Osteogenesis; Osteogenetic peptides; TGF, Transforming Growth Factor.