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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Aug 26

PMID 37629076

Authors

Petra Malavasic

Sara Polajzer

Nika Lovsin

Affiliations

Soon will be listed here.

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 () 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.

References

Dragojevic J, Zupan J, Haring G, Herman S, Komadina R, Marc J . Triglyceride metabolism in bone tissue is associated with osteoblast and osteoclast differentiation: a gene expression study. J Bone Miner Metab. 2013; 31(5):512-9. DOI: 10.1007/s00774-013-0445-x. View

Vodermaier H, Gieffers C, Maurer-Stroh S, Eisenhaber F, Peters J . TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1. Curr Biol. 2003; 13(17):1459-68. DOI: 10.1016/s0960-9822(03)00581-5. View

camernik K, Mihelic A, Mihalic R, Haring G, Herman S, Marolt Presen D . Comprehensive analysis of skeletal muscle- and bone-derived mesenchymal stem/stromal cells in patients with osteoarthritis and femoral neck fracture. Stem Cell Res Ther. 2020; 11(1):146. PMC: 7118858. DOI: 10.1186/s13287-020-01657-z. View

Yang T, Shen H, Liu A, Dong S, Zhang L, Deng F . A road map for understanding molecular and genetic determinants of osteoporosis. Nat Rev Endocrinol. 2019; 16(2):91-103. PMC: 6980376. DOI: 10.1038/s41574-019-0282-7. View

camernik K, Mihelic A, Mihalic R, Marolt Presen D, Janez A, Trebse R . Increased Exhaustion of the Subchondral Bone-Derived Mesenchymal Stem/ Stromal Cells in Primary Versus Dysplastic Osteoarthritis. Stem Cell Rev Rep. 2020; 16(4):742-754. DOI: 10.1007/s12015-020-09964-x. View

Kuo T, Chen C . Bone biomarker for the clinical assessment of osteoporosis: recent developments and future perspectives. Biomark Res. 2017; 5:18. PMC: 5436437. DOI: 10.1186/s40364-017-0097-4. View

Thornton B, Ng T, Matyskiela M, Carroll C, Morgan D, Toczyski D . An architectural map of the anaphase-promoting complex. Genes Dev. 2006; 20(4):449-60. PMC: 1369047. DOI: 10.1101/gad.1396906. View

Cappell S, Chung M, Jaimovich A, Spencer S, Meyer T . Irreversible APC(Cdh1) Inactivation Underlies the Point of No Return for Cell-Cycle Entry. Cell. 2016; 166(1):167-80. PMC: 6649667. DOI: 10.1016/j.cell.2016.05.077. View

Li M, Shin Y, Hou L, Huang X, Wei Z, Klann E . The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory. Nat Cell Biol. 2009; 10(9):1083-9. PMC: 2914158. DOI: 10.1038/ncb1768. View

10.

Tanaka-Matakatsu M, Thomas B, Du W . Mutation of the Apc1 homologue shattered disrupts normal eye development by disrupting G1 cell cycle arrest and progression through mitosis. Dev Biol. 2007; 309(2):222-35. PMC: 2080841. DOI: 10.1016/j.ydbio.2007.07.007. View

11.

Eguren M, Manchado E, Malumbres M . Non-mitotic functions of the Anaphase-Promoting Complex. Semin Cell Dev Biol. 2011; 22(6):572-8. DOI: 10.1016/j.semcdb.2011.03.010. View

12.

Sabik O, Farber C . Using GWAS to identify novel therapeutic targets for osteoporosis. Transl Res. 2016; 181:15-26. PMC: 5357198. DOI: 10.1016/j.trsl.2016.10.009. View

13.

Trajanoska K, Rivadeneira F, Kiel D, Karasik D . Genetics of Bone and Muscle Interactions in Humans. Curr Osteoporos Rep. 2019; 17(2):86-95. PMC: 6424938. DOI: 10.1007/s11914-019-00505-1. View

14.

Estrada K, Styrkarsdottir U, Evangelou E, Hsu Y, Duncan E, Ntzani E . Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet. 2012; 44(5):491-501. PMC: 3338864. DOI: 10.1038/ng.2249. View

15.

Rivadeneira F, Styrkarsdottir U, Estrada K, Halldorsson B, Hsu Y, Richards J . Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet. 2009; 41(11):1199-206. PMC: 2783489. DOI: 10.1038/ng.446. View

16.

Kim B, Ahn S, Kim H, Ikegawa S, Yang T, Guo Y . Replication of Caucasian Loci Associated with Osteoporosis-related Traits in East Asians. J Bone Metab. 2016; 23(4):233-242. PMC: 5153380. DOI: 10.11005/jbm.2016.23.4.233. View

17.

Greenspan S, von Stetten E, Emond S, Jones L, Parker R . Instant vertebral assessment: a noninvasive dual X-ray absorptiometry technique to avoid misclassification and clinical mismanagement of osteoporosis. J Clin Densitom. 2001; 4(4):373-80. DOI: 10.1385/jcd:4:4:373. View

18.

Lovsin N . Copy Number Variation and Osteoporosis. Curr Osteoporos Rep. 2023; 21(2):167-172. PMC: 10105686. DOI: 10.1007/s11914-023-00773-y. View

19.

Ivarsdottir E, Benonisdottir S, Thorleifsson G, Sulem P, Oddsson A, Styrkarsdottir U . Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density. Nat Commun. 2019; 10(1):1284. PMC: 6427039. DOI: 10.1038/s41467-019-09304-9. View

20.

Koromani F, Trajanoska K, Rivadeneira F, Oei L . Recent Advances in the Genetics of Fractures in Osteoporosis. Front Endocrinol (Lausanne). 2019; 10:337. PMC: 6559287. DOI: 10.3389/fendo.2019.00337. View