PTHrP 1-141 and 1-86 Increase In Vitro Bone Formation
Loading...
Date
2010-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier in the Journal of Surgical Research
Abstract
Background—Parathyroid hormone-related protein (PTHrP) has anabolic effects in bone, which
has led to the clinical use of N-terminal fragments of PTHrP and PTH. Since 10-20% of fractures
demonstrate healing complications and osteoporosis continues to be a debilitating disease, the
development of bone-forming agents is of utmost importance. Due to evidence that regions of
PTHrP other than the N-terminus may have bone-forming effects, this study was designed to
compare the effects of full-length PTHrP 1-141 to N-terminal PTHrP 1-86 on in vitro bone
formation.
Materials and methods—MC3T3-E1 pre-osteoblasts were treated once every 6 days for 36
days with 5, 25, and 50 pM of PTHrP 1-141 or 1-86 for 1 or 24 hours. Cells were also treated after
blocking the N-terminus, the nuclear localization sequence (NLS), and the C-terminus of PTHrP,
individually and in combination. Area of mineralization, alkaline phosphatase (ALP), and
osteocalcin (OCN) were measured.
Results—PTHrP 1-141 and 1-86 increased mineralization after 24-hr treatments, but not 1-hr.
PTHrP 1-141 was more potent than 1-86. Treatment with PTHrP 1-141 for 24-hr, but not 1-86,
resulted in a concentration-dependent increase in ALP, with no effect after 1-hr. Exposure to both
peptides for 1- or 24-hrs induced a concentration-dependent increase in OCN, with 24-hr
exceeding 1-hr. Antibody blocking revealed that the NLS and C-terminus are anabolic.
Conclusions—Both PTHrP 1-141 and 1-86 increased in vitro bone formation; however, PTHrP
1-141 was more effective. The NLS and C-terminus have anabolic effects distinct from the Nterminus.
This demonstrates the advantage of PTHrP 1-141 as a skeletal anabolic agent.
Description
Professional Biological Sciences: 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
Keywords
PTHrP 1-141, PTHrP 1-86, C-terminus, NLS, MC3T3-E1, mineralization, LCC15-MB
Citation
J Surg Res. 2010 August ; 162(2): e9–17. doi:10.1016/j.jss.2010.02.023.