Xia Han, Tian Yueyang, Lin Yile, Huang Qia, Xue Yuan
Tianjin Key Laboratory of Spine and Spinal Cord, Department of Orthopedic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Front Pharmacol. 2022 Apr 6;13:839035. doi: 10.3389/fphar.2022.839035. eCollection 2022.
Parathyroid hormone (PTH) 1-34 is the first anabolic agent approved for the treatment of osteoporosis. Preclinical evidence shows a potential association between PTH and osteosarcoma. The mechanisms mediating the bone- and neoplasm-forming effects of PTH remain incompleted understood, few studies on the role of Insulin-like growth factor-binding protein 7 (IGFBP7) in mediating the anabolic effects of PTH has been reported. Intermittent PTH administration was found to increase the expression of IGFBP7 in mesenchymal stem cells (MSCs) and pre-osteoblasts. The results indicated that the anabolic effects of PTH were interrupted when knockdown of IGFBP7, while supplementation with IGFBP7 protein could enhance the bone-forming efficacy of PTH and regulate the signaling pathways. Moreover, bone healing was accelerated by the administration of IGFBP7 along with PTH in a mouse model of fracture. The obtained results proved that IGFBP7 was necessary for the anabolic effects of PTH, and combined administration of PTH and IGFBP7 showed stronger bone-forming effects relative to administration of PTH alone.
甲状旁腺激素（PTH）1-34是首个被批准用于治疗骨质疏松症的促合成药物。临床前证据显示PTH与骨肉瘤之间存在潜在关联。介导PTH的成骨和形成肿瘤作用的机制仍未完全明确，关于胰岛素样生长因子结合蛋白7（IGFBP7）在介导PTH促合成作用中所起作用的研究报道较少。研究发现，间歇性给予PTH可增加间充质干细胞（MSC）和成骨前体细胞中IGFBP7的表达。结果表明，敲低IGFBP7会中断PTH的促合成作用，而补充IGFBP7蛋白可增强PTH的成骨功效并调节信号通路。此外，在骨折小鼠模型中，联合给予IGFBP7和PTH可加速骨愈合。所得结果证明，IGFBP7是PTH促合成作用所必需的，相对于单独给予PTH，联合给予PTH和IGFBP7显示出更强的成骨作用。
