Evaluating Osteogenic Differentiation of Osteoblastic Precursors Upon Intermittent Administration of PTH/IGFBP7

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.

Automated summary

This study found that Insulin-like growth factor-binding protein 7 (IGFBP7) plays an important role in mediating the anabolic effects of parathyroid hormone (PTH). Intermittent PTH administration increased the expression of IGFBP7 in mesenchymal stem cells (MSCs) and pre-osteoblasts. Knockdown of IGFBP7 interrupted the anabolic effects of PTH, while supplementation with IGFBP7 protein enhanced the bone-forming efficacy of PTH. In a mouse model of fracture, administration of IGFBP7 along with PTH accelerated bone healing.