An Experimental Study Of Effects On Apelin In Fracture Healing

Beyond its biological effects such as regulating vascular tone, blood pressure,angiogenesis, and cardiac remodeling, induction of proliferation, migration, inhibition ofapoptosis of cultured endothelial cells, Apelin has been shown to exert protective andregenerative actions in a variety of tissues. However, little is known about potential actions inbone regeneration. To study the effects of Apelin and its molecular mechanisms in fracturehealing, closed femur fracture models in SD rats with intramedullary nailing fixations weresuccessfully established(n=75), which were examined by X-ray score before anesthesiarecovery. The desired rats were randomly divided into five groups(n=15; respectively): thesaline negative control group、the three experimental groups of differ level(0.5、1、2μmol/L)Apelin and the positive control group of Cervus and Cucumis Polypeptide Injection (CCPI),each rat was given an equal dose (0.03mL/d for each rat) of normal saline、three differ levelApelin-13or CCPI by intramuscular injection at the point of fracture from the second day tothe end of week four after operation. One、two and four weeks after operation, bone healingwas studied including general cases of animals and X-ray score, and which was also analyzedby Bone Mineral Density (BMD) and biomechanics on week two and week four. Expressionsof Bone Morphogenetic Protein-2(BMP-2), Vascular Endothelia Growth Factor-165(VEGF),Transforming Growth Factor-β1(TGF-β1) and Type Collagen I (COL-I) in the bone calluswere examined by Western Blot on week two during fracture healing. The general cases ofanimals and X–ray scores showed a significantly higher bone volume in concentrationdependence in Apelin-13-treated animals than in saline controls, which reached its peak at1μmoL and was confirmed by a obviously higher BMD and biomechanical stiffness(n=6;P<0.01) of the periosteal callus on week two and week four after fracture and stabilization.Western Blot analyses revealed a significantly higher expression of BMP-2, VEGF-165,TGF-β1and COL-I in Apelin-13-treated animals compared to saline controls(n=3; P<0.01).Herein, we demonstrate that Apelin-13accelerates fracture healing of SD rats andinduces the expression of BMP-2, VEGF-165, TGF-β1and COL-I in the callus, which mayrepresent a promising novel treatment strategy for fractures and provide a theoretical basis for design of new drug.