Intermittent low-dose administration of recombinant human parathyroid hormone (1-34) promotes the expression of Osterix during early stage of fracture healing

Abstract

Objective To study the effects of intermittent low-dose administration of recombinant human parathyroid hormone (1-34) [rhPTH(1-34)] in the expression of Osterix (Osx) during early stage of fracture healing. Methods Forty-eight 2-month old male Sprague-Dawley rats were underwent close unilateral femoral fracture and intramedullary nail fixation. The subjects were divided into 2 equal groups randomly: treatment group undergoing subcutaneous injection of rhPTH(1-34) 10 mg/kg/d immediately after the operation and control group undergoing subcutaneous injection of normal saline of the same dose. Six rats in each group were sacrifice at 2, 7, 14, and 21 days after operation. X-ray photography study was conducted at 7, 14 and 21 days. Tissue RNA and protein were extracted from the bone tissues of bilateral femurs and the expression levels of Osx mRNA and protein were evaluated via real time quantitative PCR and Western-blotting. Results Fracture healing was significant at 14 days after operation, and the progress of fracture healing was better in the rhPTH(1-34) group than in the control group at 14 and 21 days. The relative expression of Osx mRNA and protein in the fractured femurs of the rhPTH(1-34) group (5.02±0.5 and 10.03±0.8 for Osx mRNA, 3164.03±131 and 3509.02±126 for protein) at 14 and 21 days after the operation were significantly higher than those of the control group (2.30±0.4 and 4.01±0.7 for Osx mRNA, 1053.04±121 and 2721.03±123 for protein). However, there was no significant difference at 2 and 7 days after operation between the rhPTH(1-34) and control group. Conclusion Intermittent low-dose administration of rhPTH(1-34) up-regulates the expression levels of osteogenesis-specific Osx mRNA and protein in rats. It will accelerate the early phase of fracture healing process. Key words: Fracture healing; Teriparatide; Gene expression