Catholic iPSC Research Center (CiRC), CiSTEM Laboratory, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.
Department of Biomedicine & Health Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 07345, Korea.
Int J Mol Sci. 2021 Aug 23;22(16):9069. doi: 10.3390/ijms22169069.
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.
骨质疏松症通常通过长期使用抗骨质疏松药物治疗；然而，药物依从性差和不良反应限制了它们的治疗效果。甲状旁腺激素相关蛋白（PTHrP）是正常骨形成和重塑所必需的；因此，它可以用作抗骨质疏松药物。在这里，我们使用微环载体开发了一种递送由 PTHrP 蛋白的两个区域（1-34 和 107-139）组成的单一肽的平台；mcPTHrP 1-34+107-139。我们还将 mcPTHrP 1-34+107-139 转染到人骨髓间充质干细胞（MSCs）中，并生成产生 Thru 1-34+107-139 的工程 MSC（eMSC）作为替代递送系统。通过卵巢切除术在 12 周龄 C57BL/6 雌性小鼠中诱导骨质疏松症。然后用两种系统治疗去卵巢（OVX）小鼠；（1）mcPTHrP 1-34+107-139 静脉内给药三次（每周一次）；（2）eMSCs 腹腔内给药两次（第 4 周和第 6 周）。与对照 OVX 小鼠相比，mcPTHrP 1-34+107-139 治疗组表现出更好的小梁骨结构质量，增加了骨形成，减少了骨吸收。在 eMSC 治疗的 OVX 小鼠中也观察到了类似的结果。总之，这些结果为使用微环技术递送 PTHrP 1-34+107-139 治疗骨质疏松症提供了实验证据。
