Regulation of Osteoblast Differentiation by Affinity Peptides of TGF-β1 Identified via Phage Display Technology

Transforming growth factor β1 (TGF-β1) plays a dual role in bone formation. In addition to promoting early differentiation of osteogenesis, it may also lead to uncontrolled extracellular matrix synthesis, inhibition of bone mineralization in the late stage, and aberrant bone remodeling. In this work, affinity peptides of TGF-β1 (Tβms) were identified from a phage display library to modify the TGF-β1 signal transduction. Tβms with more order and compact structures tended to have a higher affinity to TGF-β1 but maintained a greater immunoreactivity of TGF-β1. Tβms promoted the early osteoblast proliferation and had a negligible effect on the osteoblast differentiation. In synergy with exogenous TGF-β1, Tβms reduced the alkaline phosphatase (ALP) mRNA expression but significantly improved the expression of osteocalcin (OCN), along with impaired phosphorylation of Smad2/3. Moreover, osteoblasts showed an overall increase in ALP activity and Ca deposition than the blank control. These results demonstrated that Tβms could weaken the inhibition of TGF-β1 on osteogenic differentiation in the late stage. Depending on the impact features of Tβms on TGF-β1 response, these peptides may help to modify the implant surfaces to optimize the bone remodeling of interface, and be of interest in design of multidomain peptides.