Ablation of the Mammalian Lectin Galectin-8 Induces Bone Defects in Mice

Mice overexpressing galectin-8 (gal-8 Tg), a secreted mammalian lectin, exhibit enhanced bone turnover and reduced bone mass, similar to cases of post-menopausal osteoporosis. Gal-8 knockout (KO) mice have increased bone mass accrual at young age, but exhibit accelerated bone loss during adulthood. These phenotypes can be attributed to gal-8-mediated increase in RANKL expression that promotes osteoclastogenesis, combined with direct inhibition of osteoblasts differentiation, evident by reduced BMP signaling, SMAD phosphorylation, and reduced expression of osteoblasts differentiation markers OSX, OCN, RUNX2, DMP-1 and ALP. Gal-8 mRNA positively correlates with the mRNA levels of osteoclastogenic markers RANKL, TRAP and CTSK in human femurs. Collectively, these findings identify gal-8 as a new physiological player in the regulation of bone mass.

6

Vinik Y, Shatz-Azoulay H, Hiram-Bab S, Kandel L, Gabet Y, Rivkin G, Zick Y