Lack of anabolic response to skeletal loading in mice with targeted disruption of the pleiotrophin gene

Background. In a previous study we showed, using the whole genome microarray approach, that pleiotrophin (PTN) expression was increased by 4-fold in response to mechanical loading (ML) in a good responder C57BL/6J (B6) mice. To address PTN role in mediating ML effects on bone formation, we first evaluated time course effects of ML on expression levels of PTN gene using real time RT-PCR in 10 week female B6 mice. A 9 N load was applied using a four-point bending device at 2 Hz frequency for 36 cycles, once per day for 2, 4 and 12 days on the right tibia and the left tibia was used as internal control. Findings. Four-point bending caused an acute increase in PTN expression (2-fold) within 2 days of loading and further increased (3-6 fold) with continued loading. This increase was also seen in 16 and 36-week old mice. Based on these findings, we next used PTN knockout (KO) mice to evaluate the cause and effect relationship. Quantitative analysis showed that two weeks of ML induced changes in vBMD and bone size in the PTN KO mice (8% and 6% vs. non-loaded bones) were not significantly different from control mice (11% and 8% in vBMD and bone size vs. non-loaded bones). Conclusion. Our results imply that PTN is not a key upstream mediator of the anabolic effects of ML on the skeleton.