Engraftment and bone mass are enhanced by PTHrP 1-34 in ectopically transplanted vertebrae (vossicle model) and can be non-invasively monitored with bioluminescence and fluorescence imaging.
Evidence exists that parathyroid hormone-related protein (PTHrP) 1-34 may be more anabolic in bone than parathyroid hormone 1-34. While optical imaging is growing in popularity, scant information exists on the relationships between traditional bone imaging and histology and bioluminescence (BLI) and fluorescence (FLI) imaging. We aimed to evaluate the effects of PTHrP 1-34 on bone mass and determine if relationships existed between radiographic and histologic findings in bone and BLI and FLI indices. Vertebrae (vossicles) from mice coexpressing luciferase and green fluorescent protein were implanted subcutaneously into allogenic nude mice. Transplant recipients were treated daily with saline or PTHrP 1-34 for 4 weeks. BLI, FLI, radiography, histology, and µCT of the vossicles were performed over time. PTHrP 1-34 increased bioluminescence the most after 2 weeks, fluorescence at all time points, and decreased the time to peak bioluminescence at 4 weeks (P ≤ 0.027), the latter of which suggesting enhanced engraftment. PTHrP 1-34 maximized vertebral body volume at 4 weeks (P < 0.0001). The total amount of bone observed histologically increased in both groups at 2 and 4 weeks (P ≤ 0.002); however, PTHrP 1-34 exceeded time-matched controls (P ≤ 0.044). A positive linear relationship existed between the percentage of trabecular bone and (1) total bioluminescence (r = 0.595; P = 0.019); (2) total fluorescence (r = 0.474; P = 0.074); and (3) max fluorescence (r = 0.587; P = 0.021). In conclusion, PTHrP 1-34 enhances engraftment and bone mass, which can be monitored non-invasively by BLI and FLI.
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Blake Eason
BE
Hildreth
Small Animal Imaging Center, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.
Michelle M
MM
Williams
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Katarzyna A
KA
Dembek
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Krista M
KM
Hernon
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA.
Thomas J
TJ
Rosol
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH, 43210, USA. toribio.1@osu.edu.
Ramiro E
RE
Toribio
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015519:Bone Density / Q000187:drug effects*; D016025:Bone Transplantation; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D061848:Optical Imaging; D010012:Osteogenesis / Q000187:drug effects; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*
D000959:Antihypertensive Agents; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; C054296:parathyroid hormone-related protein (1-34)
Bioluminescence; Fluorescence; PTHrP; Transplantation; Vossicle