Loss of Lgals3 Protects Against Gonadectomy-Induced Cortical Bone Loss in Mice

• DOI: 10.1007/s00223-019-00630-0
• Publication Date: 2019-11-19T20:01:33Z
• Authors: Kevin A. Maupin; Daniel Dick; Johan Lee; Bart O. Williams
• Keywords: Male; Mice, Knockout; 0303 health sciences; Galectin 3; Dihydrotestosterone; Estrogens; Mice; 03 medical and health sciences; Cancellous Bone; Androgens; Body Composition; Cortical Bone; Animals; Osteoporosis; Female; Castration

Sex hormone deprivation commonly occurs following menopause in women or after androgen-depletion during prostate cancer therapy in men, resulting in rapid bone turnover and loss of bone mass. There is a need to identify novel therapies to improve bone mass in these conditions. Previously, we identified age- and sex-dependent effects on bone mass in mice with deletion of the gene encoding the β-galactoside binding lectin, galectin-3 (Lgals3-KO). Due to the influence of sex on the phenotype, we tested the role of sex hormones, estrogen (β-estradiol; E2), and androgen (5α-dihydroxytestosterone; DHT) in Lgals3-KO mice. To address this, we subjected male and female wild-type and Lgals3-KO mice to gonadectomy ± E2 or DHT rescue and compared differential responses in bone mass and bone formation. Following gonadectomy, male and female Lgals3-KO mice had greater cortical bone expansion (increased total area; T.Ar) and reduced loss of bone area (B.Ar). While T.Ar and B.Ar were increased in response to DHT in wild-type mice, DHT did not alter these parameters in Lgals3-KO mice. E2 rescue more strongly increased B.Ar in Lgals3-KO compared to wild-type female mice due to a failure of E2 to repress the increase in T.Ar following gonadectomy. Lgals3-KO mice had more osteoblasts relative to bone surface when compared to wild-type animals in sham, gonadectomy, and E2 rescue groups. DHT suppressed this increase. This study revealed a mechanism for the sex-dependency of the Lgals3-KO aging bone phenotype and supports targeting galectin-3 to protect against bone loss associated with decreased sex hormone production.