Anaphase-promoting complex subunit 1 associates with bone mineral density in human osteoporotic bone

Petra Malavašič (Author), Sara Polajžer (Author), Nika Lovšin (Author)

Abstract

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 anaphase-promoting complex subunit 1 (ANAPC1) gene (p = 1.5 × 10−9). Here, we functionally evaluate the role of ANAPC1 in bone remodelling by examining the expression of ANAPC1 in human bone and muscle tissues and during the osteogenic differentiation of human primary mesenchymal stem cells (MSCs). The expression of ANAPC1 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 ANAPC1 changes during the osteogenic differentiation process of human MSCs. Moreover, the silencing of ANAPC1 in human osteosarcoma (HOS) cells reduced RUNX2 expression, suggesting that ANAPC1 affects osteogenic differentiation through RUNX2. Altogether, our results indicate that ANAPC1 plays a role in bone physiology and in the development of osteoporosis.

Keywords

kompleksna podenota 1, ki spodbuja anafazo;osteogeneza;mineralizacija osteoblastov;tvorba kosti;mineralna gostota kosti;anaphase-promoting complex subunit 1;osteoporosis;osteogenesis;osteoblast mineralisation;bone formation;bone mineral density;

Data

Language:	English
Year of publishing:	2023
Typology:	1.01 - Original Scientific Article
Organization:	UL FFA - Faculty of Pharmacy
UDC:	616.71-007.234
COBISS:	162450947
ISSN:	1422-0067
Views:	13
Downloads:	0
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	Slovenian
Secondary keywords:	Osteoporoza;Kosti;
Type (COBISS):	Article
Pages:	16 str.
Volume:	ǂVol. ǂ24
Issue:	ǂno. ǂ16, art. 12895
Chronology:	2023
DOI:	10.3390/ijms241612895
ID:	19861971