Increased Potential of Bone Formation With Intravenous Injection of Parathyroid Hormone-minicircle DNA Vector 

Background: Osteoporosis is usually treated with long-term usage of anti-osteoporotic agents. However, poor drug compliance and emerging side effects sometimes are limitations for the treatment of osteoporosis. Parathyroid hormone-related protein (PTHrP) is needed for normal bone formation and remodeling. We attempted a new method using minicircle vectors (mc) encoding PTHrP analogs. Methods: : We generated mc encoding the infusion of PTHrP 1-34 with 107-139 (mc 1-34+107-139). Ovariectomized (OVX) model was induced in 12-week-old C57BL/6 female mice. mc 1-34+107-139 was administered three times weekly via intravenous injections. Results: : mc 1-34+107-139 significantly increased bone formation compared with the OVX group and decreased the bone resorption. PTHrP mc DNA vector was effective in increasing the quality of trabecular bone structure. Conclusions: : These results provide experimental evidence for the therapeutic potential of minicircle DNA vectors in OVX model. This study is a first attempted proof-of-concept gene therapy using minicircle vectors for the treatment of osteoporosis.