Parathyroid Hormone Related Peptide In The Role Of Promoting Fracture Healing And Mechanism Research

OBJECTIVE:To determine the lack of endogenous PTHrP and PTHrP exogenous administration fracture healing, and to investigate the role of PTHrP as well as the underlying mechanism involved in the process of fracture healing.METHODS:8-week-old wild-type littermates (WT) and heterozygous PTHrP (PTHrP+/-) mice were established to the standardized model of femur shaft fractures and randomly divided into four groups:WT control group, PTHrP+/- control group, WT treatment group, PTHrP+ /-therapy group(n= 6). The mice of treatment group were infused with PTHrPl-86(80 μg·kg-1·d-1, ih.), at the same time,the mice of control group were given normal saline. After two weeks, the mice were confirmed to do X-ray photography and the Micro-CT scanning, in order to do some bone callus tissue imaging analysis; Osteoblasts in the callus were determined by histological staining, histochemical staining and immunohistochemical staining; the expression levels of genes related to bone cells were determined by real-time fluorescent RT-PCR; Expression of the osteoblast-associated protein was determined by Western blot analysis.RESULTS:Compared with WT control group, the volume total bone and bone callus of saline-treated mice PTHrP+/-was significantly reduced (P<0.05), the number of the osteoblast in per unit area was reduced (P<0.05), positive area of collagen I was reduced (P<0.05); gene expression levels of Osteocalcin (OCN), Alkaline phosphatase (ALP), runt-related transcription factor 2(RUNX2) and Collagen I (COL-1) were reduced (P<0.05),as well as Runx2 and IGF-1 protein (P< 0.05). In the same genotype, compared with control group, treatment group significantly increased bone callus, the number of osteoblasts in per unit area, as well as the positive area of collagen I, and upregulated osteoblast-related genes and the expression of protein.CONCLUSIONS:Lack of endogenous PTHrP was able to delay fracture healing, while administration exogenous PTHrP can correct this effect and promote fracture healing in normal mice. PTHrP may promot fracture healing by accelerating osteoblast proliferation and activation, So that accelerate the formation of callus and cartilage callus.