WNT16 overexpression partly protects against glucocorticoid-induced bone loss

Therapeutic use of glucocorticoids (GCs) is a major cause of secondary osteoporosis but the molecular mechanisms responsible for the deleterious effects of GCs in bone are only partially understood. WNT16 is a crucial physiological regulator of bone mass and fracture susceptibility and we hypothesize that disturbed WNT16 activity might be involved in the deleterious effects of GC in bone. Twelve-week-old female Obl-Wnt16 mice (WNT16 expression driven by the rat procollagen type I α 1 promoter) and WT littermates were treated with prednisolone (7.6 mg/kg/day) or vehicle for 4 weeks. We first observed that GC-treatment decreased the Wnt16 mRNA levels in bone of female mice (-56.4 {plus minus} 6.1% compared to vehicle, P < 0.001). We next evaluated if WNT16 overexpression protects against GC-induced bone loss. DXA analyses revealed that GC-treatment decreased total body bone mineral density (BMD) in WT mice ( 3.9 {plus minus} 1.2%, P = 0.028), but not in Obl-Wnt16 mice (+1.3 {plus minus} 1.4%, non-significan...