Bone Abstracts

Objectives: Lysophosphatidic acid (LPA) is a potent lipid growth factor which possess several G protein-coupled receptors LPA1-6. We have recently demonstrated that LPA1 receptor-invalidated mice display abnormal bone development and osteoporosis, suggesting abnormal endochondral ossification. We have here further studied the growth plates of LPA1 receptor-invalidated mice.

Methods: We performed a microscopic and immuno-histochemistry analysis of the femoral and tibia bones of 1–4 weeks old LPA1(−/−) mice raised on a C57BL/6 background.

Results: Microscopic analysis demonstrated marked narrowing of the growth plate of the long bones. The proximal tibia was significantly affected with a 27.7% decrease. In the proximal growth plate of the femur, the reserve zone was relatively preserved in LPA1(−/−) mice. In contrast, the columnar proliferative zone was clearly decreased. The hypertrophic zone was not significantly affected. Quantification of the different zones showed a significant decrease in the proliferative zone of LPA1(−/−) mice, especially in the tibia growth plates which were diminished by 37.8%. Other abnormalities were also detectable in the growth plate of LPA1(−/−) mice. The columnar structures were less regular and less organized in comparison to WT. Application of Ki67 antibody to quantify the mitotic index in the proliferative zone, cell proliferation appeared decreased by 31% in the proliferative zone of LPA1(−/−) mice.

Conclusion: These results suggest that LPA1 receptor is involved in the development of growth plate by influencing the proliferating rate of chondrocytes. LPA and LPA1 are new factors potentially involved in patho-physiological situations where endochondral ossification is impaired.