TP508 accelerates fracture repair by promoting cell growth over cell death.
TP508 is a synthetic 23-amino acid peptide representing a receptor-binding domain of human thrombin. We have previously shown that a single injection of TP508 accelerates fracture healing in a rat femoral fracture model. To understand how TP508 acts at the protein level during fracture healing, we compared the translational profiles between saline-control and fractured femur at six time points after TP508 treatment using the second generation of BD Clontechtrade mark Antibody Microarray. Here, we demonstrate that TP508 accelerates fracture healing by modulating expression levels of proteins primarily involved in the functional categories of cell cycle, cellular growth and proliferation, and cell death. The majority of those proteins are physically interrelated and functionally overlapped. The action of those proteins is highlighted by a central theme of promoting cell growth via balance of cell survival over cell death signals. This appears to occur through the stimulation of several bone healing pathways including cell cycle-G1/S checkpoint regulation, apoptosis, JAK/STAT, NF-kappaB, PDGF, PI3K/AKT, PTEN, and ERK/MAPK.
Li
Xinmin
X
College of Animal Science and Technology, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
Wang
Hali
H
Touma
Edward
E
Qi
Yuchen
Y
Rousseau
Emma
E
Quigg
Richard J
RJ
Ryaby
James T
JT
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005264:Femoral Fractures / Q000628:therapy; D017102:Fracture Healing / Q000187:drug effects*; D020869:Gene Expression Profiling; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013917:Thrombin / Q000494:pharmacology*
D010446:Peptide Fragments; C412222:rusalatide acetate; D013917:Thrombin