Targeted Overexpression of in Osteoblasts Increases Trabecular Bone Mass by Stimulating Osteogenesis at the Expense of Adipogenesis in Mice.

Mice lacking () manifest reduced trabecular bone mass. However, the impact of expression in osteoblasts in vivo remains understudied. Herein, we generated osteoblast-specific transgenic (Tg) mice expressing and characterized their skeletal phenotype. Micro-CT analyses of the distal metaphysis of the femur showed a 50% and a 38% increase in trabecular bone mass in Tg male and female mice, respectively, due to a significant increase in trabecular number and a reduction in trabecular separation. Histomorphometry and serum biomarker studies uncovered that increased trabecular bone mass in Tg mice was the consequence of enhanced bone formation. Accordingly, an abundance of bone formation (, ), but not bone resorption (), markers were augmented in the femurs of Tg mice. Since the trabecular bone density is known to inversely correlate with the amount of marrow adipose tissue (MAT), we measured the MAT in osmium-tetroxide-labeled bones by micro-CT scanning. We found 86% less MAT in the proximal tibia of the Tg males. Consistently, the expression levels of the adipogenic markers, and , were 50% lower in the femurs of the Tg males. Our data are consistent with the possibility that claudin11 exerts anabolic effects in osteoblastic lineage cells that act via promoting the differentiation of marrow stem cells towards osteoblasts at the expense of adipocytes.