Multiple Mechanisms Explain Genetic Effects at the CPED1-WNT16 Bone Mineral Density Locus

Curr Osteoporos Rep. 2023 Apr;21(2):173-183. doi: 10.1007/s11914-023-00783-w. Epub 2023 Mar 21.

Abstract

Purpose of review: Chromosome region 7q31.31, also known as the CPED1-WNT16 locus, is robustly associated with BMD and fracture risk. The aim of the review is to highlight experimental studies examining the function of genes at the CPED1-WNT16 locus.

Recent findings: Genes that reside at the CPED1-WNT16 locus include WNT16, FAM3C, ING3, CPED1, and TSPAN12. Experimental studies in mice strongly support the notion that Wnt16 is necessary for bone mass and strength. In addition, roles for Fam3c and Ing3 in regulating bone morphology in vivo and/or osteoblast differentiation in vitro have been identified. Finally, a role for wnt16 in dually influencing bone and muscle morphogenesis in zebrafish has recently been discovered, which has brought forth new questions related to whether the influence of WNT16 in muscle may conspire with its influence in bone to alter BMD and fracture risk.

Keywords: Fracture; GWAS, BMD; Genetics; Osteoporosis; WNT signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Bone Density / genetics
  • Fractures, Bone* / genetics
  • Mice
  • Osteoporosis* / genetics
  • Wnt Proteins / genetics
  • Zebrafish
  • Zebrafish Proteins / genetics

Substances

  • Wnt Proteins
  • Wnt16 protein, mouse
  • wnt16 protein, zebrafish
  • Zebrafish Proteins
  • Cped1 protein, mouse