Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Department of Mechanical Engineering, University of Delaware, Newark, DE 19716, USA.
Int J Mol Sci. 2020 Jul 10;21(14):4874. doi: 10.3390/ijms21144874.
Osteoporosis is a bone disease that has no definite cure. Current treatments for osteoporosis are divided into two categories: anti-resorptive and anabolic. However, these treatments are not perfect and have considerable risks. In addition, bone quality often declines over time with these treatments. We designed a peptide, CK2.3, that has both anabolic and anti-resorptive effects on bone. We reported that CK2.3 induced osteoblastic mineralization, promoted bone formation, and suppressed osteoclastogenesis in vivo. The effect of CK2.3 to rescue an osteoporosis phenotype model has never been shown. In this study, we demonstrated the effect of CK2.3 in ovariectomized rats, a standard model of osteoporosis. We systemically injected CK2.3 at 2.3 µg/kg each day for five consecutive days. Micro-computed tomography indicated that CK2.3 increased bone mineral density, (bone volume/tissue volume) BV/TV and (trabecular number) TbN, and decreased (trabecular space) TbSp in the femoral head. Similarly, single photon absorptiometry showed that treatment with CK2.3 increased bone mineral density in the lumbar spine and the pelvis. Additionally, we observed increased femoral shaft stiffness with ovariectomized rats treated with CK2.3. We also detected no significant changes in the weight of organs such as the heart, lung, liver, kidney, and spleen. An advantage of CK2.3 over current treatments was that it not only promoted bone formation but also improved fracture resistance. In conclusion, we demonstrated CK2.3 as a new anabolic treatment for osteoporosis.
骨质疏松症是一种骨骼疾病，目前尚无明确的治愈方法。目前治疗骨质疏松症的方法分为两类：抗吸收和合成代谢。然而，这些治疗方法并不完美，存在相当大的风险。此外，随着时间的推移，这些治疗方法往往会导致骨质量下降。我们设计了一种肽，CK2.3，它对骨骼具有抗吸收和合成代谢的双重作用。我们报告说 CK2.3 诱导成骨细胞矿化，促进骨形成，并在体内抑制破骨细胞生成。CK2.3 挽救骨质疏松表型模型的效果从未被证明过。在这项研究中，我们展示了 CK2.3 在去卵巢大鼠（骨质疏松症的标准模型）中的作用。我们每天系统地注射 2.3µg/kg 的 CK2.3，连续 5 天。微计算机断层扫描表明，CK2.3 增加了股骨头的骨矿物质密度、（骨体积/组织体积）BV/TV 和（小梁数）TbN，减少了（小梁间距）TbSp。同样，单光子吸收法显示，用 CK2.3 治疗可增加腰椎和骨盆的骨矿物质密度。此外，我们观察到用 CK2.3 治疗的去卵巢大鼠股骨干的刚度增加。我们还没有发现心脏、肺、肝、肾和脾等器官的重量有明显变化。CK2.3 相对于现有治疗方法的一个优势是，它不仅促进了骨形成，而且提高了骨折抵抗力。总之，我们证明了 CK2.3 是一种治疗骨质疏松症的新的合成代谢治疗方法。
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