Apelin-13 deficiency alters cortical bone geometry, organic bone matrix, and inhibits Wnt/β-catenin signaling.

Adipokines play key roles in the regulation of obesity, type 2 diabetes mellitus, and bone growth. As a newly discovered hormone in the adipokines family, the precise role of Apelin-13 on bone metabolism is not yet clear. Apelin-13 and 25(OH)D3 expression were detected in freshly isolated serum of healthy individuals and osteoporosis patients with ELISA method. Apelin-13 deficient mice were set up and cortical bone geometry was measured with micro-computed tomography (Micro-CT) at 5 months old, then profile of organic bone matrix genes was detected with quantitative Real-Time PCR (qRT-PCR). Wnt/β-catenin signaling molecules were assayed in primary osteocytes isolated from neonatal calvarias. Apelin-13 and 25(OH)D3 showed decreased expression in osteoporosis patients. Five-month-old Apelin deficient mice exhibited decreased total and bone marrow cavity area and periosteal and endocortical bone surface. Deficiency of Apelin-13 downregulated collagen maturation associated genes (loxl3 and loxl4) and Wnt/β-catenin signaling, while loxl2 was upregulated, all of which indicated that Apelin-13 could play a role in regulating skeletal homeostasis. The decrease in bone formation in Apelin-13 deficient mice is associated with downregulation of organic bone matrix genes and Wnt/β-catenin signaling molecules, all of these indicate that association of Apelin-13 with bone mineral density (BMD) could be mediated by Wnt/β-catenin pathway.