Effects of pleiotrophin (PTN) over-expression on mouse long bone development, fracture healing and bone repair.

Pleiotrophin (PTN) was found to have potent effects on regulation of osteoblast recruitment, proliferation and differentiation. The present study examined the long-term effects of targeted PTN over-expression on bone development and repair in a transgenic mouse model. Femurs and tibiae from the PTN transgenic mice and the wild type mice at age 1, 2, 4, 6, 12 and 24 months were collected, and examined by radiography, peripheral quantitative computed tomography (pQCT), histology and mechanical testing. Age-matched PTN and the control mice received a standardized femoral fracture, followed by regular x-rays and sacrificed at day 16 post-fracture for histology examination. A cortical hole was drilled on the tibiae of age-matched PTN and wild type mice, collagen sponge with either saline, 100 ng of rhBMP-2 or rhPTN was implanted in the holes, and animals were sacrificed 10 days later, subject to pQCT and histology examinations. During early stages of bone development, the PTN mice had advanced bone growth in length and maturation, but the difference diminished in later life. The fracture healing was impaired in the PTN mice, and there was delayed callus formation and remodelling. The cortical holes treated with BMP-2 in the PTN mice had significantly less trabecular bone formation. The current study confirmed that the targeted PTN over-expression in mouse bone has moderate enhancing effects on early bone development; but the bones become brittle in later life. Fracture healing was impaired in the adult PTN mice and this may be due to inhibitory effects of PTN over-expression on BMP-2 mediated bone induction.