Enhanced cortical bone expansion in Lgals3-deficient mice during aging

Abstract

Imbalances between bone formation and bone resorption, which can occur due to aging or sex hormone deprivation, result in decreased bone mass and an increased risk of fracture. Previous studies have suggested that the β-galactoside binding lectin, galectin-3, is involved in bone remodeling. We compared bone parameters of mice having null alleles of the galectin-3 gene (Lgals3-KO) with those of their wild-type littermates. Lgals3 deficiency increased cortical bone expansion at 36 weeks (wk) and preserved or enhanced bone mass in both male and female mutant mice. In addition, female Lgals3-KO mice were protected from age-related loss of trabecular bone. Histomorphometry and ex vivo primary cell differentiation assays showed increased osteoblastogenesis with little-to-no effect on osteoclastogenesis, suggesting the increased bone mass phenotype is primarily due to increased anabolism. Our study identifies galectin-3 as a negative regulator of bone formation and suggests that disruption of galectin-3 may be useful in preventing bone loss during aging.

Osteoporosis: A knockout for stronger bones

Researchers have identified a promising new drug target to reduce bone loss during aging, a protein called galectin-3. Bones undergo lifelong remodeling via resorption of old bone and generation of new bone. With aging, the balance tips towards resorption, weakening bones. Galectin-3 was known to be involved in bone remodeling and levels increased with age. Bart Williams and co-workers at the Van Andel Research Institute in Grand Rapids, USA, investigated whether the age-related increase in galectin-3 increased bone loss. Using mice lacking the gene encoding galectin-3, the researchers measured bone mass at different ages. In older mice, bone mass was preserved or even enhanced. Further investigation of bone cells showed the increase was probably due to increased bone formation, rather than decreased bone resorption. The researchers conclude that disrupting galectin-3 may help to prevent aging-related bone loss.

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