Anaphase-Promoting Complex Subunit 1 Associates with Bone Mineral Density in Human Osteoporotic Bone.

Genome-wide association studies (GWAS) are one of the most common approaches to identify genetic loci that are associated with bone mineral density (BMD). Such novel genetic loci represent new potential targets for the prevention and treatment of fragility fractures. GWAS have identified hundreds of associations with BMD; however, only a few have been functionally evaluated. A locus significantly associated with femoral neck BMD at the genome-wide level is intronic SNP rs17040773 located in the intronic region of the () gene ( = 1.5 × 10). Here, we functionally evaluate the role of in bone remodelling by examining the expression of in human bone and muscle tissues and during the osteogenic differentiation of human primary mesenchymal stem cells (MSCs). The expression of was significantly decreased 2.3-fold in bone tissues and 6.2-fold in muscle tissue from osteoporotic patients as compared to the osteoarthritic and control tissues. Next, we show that the expression of changes during the osteogenic differentiation process of human MSCs. Moreover, the silencing of in human osteosarcoma (HOS) cells reduced expression, suggesting that affects osteogenic differentiation through . Altogether, our results indicate that plays a role in bone physiology and in the development of osteoporosis.