PMID- 34445802 OWN - NLM STAT- MEDLINE DCOM- 20210916 LR - 20210916 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 16 DP - 2021 Aug 23 TI - Increased Potential of Bone Formation with the Intravenous Injection of a Parathyroid Hormone-Related Protein Minicircle DNA Vector. LID - 10.3390/ijms22169069 [doi] LID - 9069 AB - 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. FAU - Kim, Jang-Woon AU - Kim JW AD - Catholic iPSC Research Center (CiRC), CiSTEM Laboratory, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. AD - Department of Biomedicine & Health Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea. FAU - Park, Narae AU - Park N AD - Catholic iPSC Research Center (CiRC), CiSTEM Laboratory, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. AD - Department of Biomedicine & Health Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea. FAU - Kang, Jaewoo AU - Kang J AD - Catholic iPSC Research Center (CiRC), CiSTEM Laboratory, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. AD - Department of Biomedicine & Health Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea. FAU - Kim, Yena AU - Kim Y AD - Catholic iPSC Research Center (CiRC), CiSTEM Laboratory, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. AD - Department of Biomedicine & Health Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea. FAU - Jung, Hyerin AU - Jung H AD - Catholic iPSC Research Center (CiRC), CiSTEM Laboratory, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. AD - Department of Biomedicine & Health Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea. FAU - Rim, Yeri Alice AU - Rim YA AUID- ORCID: 0000-0001-9541-3075 AD - Catholic iPSC Research Center (CiRC), CiSTEM Laboratory, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. AD - Department of Biomedicine & Health Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea. FAU - Ju, Ji Hyeon AU - Ju JH AUID- ORCID: 0000-0002-1381-5466 AD - Catholic iPSC Research Center (CiRC), CiSTEM Laboratory, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. AD - Department of Biomedicine & Health Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea. AD - Department of Internal Medicine, Division of Rheumatology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea. LA - eng GR - HI14C3417, H18C1178/Korea Healthcare Technology R&D project, Ministry for Health, Welfare & Family Affairs, Re-public of Korea/ GR - No. 2019R1A5A2027588/National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ GR - No. 2020R1A2C3004123/National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)/ PT - Journal Article DEP - 20210823 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Parathyroid Hormone-Related Protein) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Bone Density/drug effects MH - Bone Resorption/*drug therapy MH - Cell Line MH - DNA/*administration & dosage MH - Female MH - HEK293 Cells MH - Humans MH - Injections, Intravenous/methods MH - Mesenchymal Stem Cells/drug effects MH - Mice MH - Mice, Inbred C57BL MH - Osteogenesis/*drug effects MH - Osteoporosis/drug therapy MH - Ovariectomy/methods MH - Parathyroid Hormone-Related Protein/*administration & dosage PMC - PMC8396456 OTO - NOTNLM OT - minicircle DNA vector OT - osteoporosis OT - ovariectomized mice OT - parathyroid hormone-related protein OT - trabecular bone structure COIS- There are no financial conflict of interest to disclosure. The authors declare no competing interests. EDAT- 2021/08/28 06:00 MHDA- 2021/09/18 06:00 PMCR- 2021/08/23 CRDT- 2021/08/27 01:25 PHST- 2021/07/16 00:00 [received] PHST- 2021/08/14 00:00 [revised] PHST- 2021/08/18 00:00 [accepted] PHST- 2021/08/27 01:25 [entrez] PHST- 2021/08/28 06:00 [pubmed] PHST- 2021/09/18 06:00 [medline] PHST- 2021/08/23 00:00 [pmc-release] AID - ijms22169069 [pii] AID - ijms-22-09069 [pii] AID - 10.3390/ijms22169069 [doi] PST - epublish SO - Int J Mol Sci. 2021 Aug 23;22(16):9069. doi: 10.3390/ijms22169069.