Increased Potential of Bone Formation with the Intravenous Injection of a Parathyroid Hormone-Related Protein Minicircle DNA Vector

Osteoporosis is commonly treated via the long-term usage of anti-osteoporotic agents; however, poor drug compliance and undesirable side effects limit their treatment efficacy. The parathyroid hormone-related protein (PTHrP) is essential for normal bone formation and remodeling; thus, may be used as...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-08, Vol.22 (16), p.9069
Main Authors: Kim, Jang-Woon, Park, Narae, Kang, Jaewoo, Kim, Yena, Jung, Hyerin, Rim, Yeri Alice, Ju, Ji Hyeon
Format: Article
Language:English
Subjects:
Biomedical materials
Bone density
Bone growth
Bone remodeling
Bone resorption
Bones
Cancellous bone
Estrogens
FDA approval
Fractures
Gene therapy
Intravenous administration
Localization
Mesenchyme
Metabolism
minicircle DNA vector
Osteogenesis
Osteoporosis
ovariectomized mice
Ovariectomy
Parathyroid
Parathyroid hormone
Parathyroid hormone-related protein
Peptides
Protein expression
Proteins
Spleen
Stem cell transplantation
Stem cells
trabecular bone structure
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Summary:Osteoporosis is commonly treated via the long-term usage of anti-osteoporotic agents; however, poor drug compliance and undesirable side effects limit their treatment efficacy. The parathyroid hormone-related protein (PTHrP) is essential for normal bone formation and remodeling; thus, may be used as an anti-osteoporotic agent. Here, we developed a platform for the delivery of a single peptide composed of two regions of the PTHrP protein (1–34 and 107–139); mcPTHrP 1–34+107–139 using a minicircle vector. We also transfected mcPTHrP 1–34+107–139 into human mesenchymal stem cells (MSCs) and generated Thru 1–34+107–139-producing engineered MSCs (eMSCs) as an alternative delivery system. Osteoporosis was induced in 12-week-old C57BL/6 female mice via ovariectomy. The ovariectomized (OVX) mice were then treated with the two systems; (1) mcPTHrP 1–34+107–139 was intravenously administered three times (once per week); (2) eMSCs were intraperitoneally administered twice (on weeks four and six). Compared with the control OVX mice, the mcPTHrP 1–34+107–139-treated group showed better trabecular bone structure quality, increased bone formation, and decreased bone resorption. Similar results were observed in the eMSCs-treated OVX mice. Altogether, these results provide experimental evidence to support the potential of delivering PTHrP 1–34+107–139 using the minicircle technology for the treatment of osteoporosis.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22169069