RESUMEN
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.
Asunto(s)
Fracturas Óseas , Osteoporosis , Animales , Ratones , Densidad Ósea/genética , Fracturas Óseas/genética , Osteoporosis/genética , Proteínas Wnt/genética , Pez Cebra , Proteínas de Pez Cebra/genéticaRESUMEN
Bone and muscle are coupled through developmental, mechanical, paracrine, and autocrine signals. Genetic variants at the CPED1-WNT16 locus are dually associated with bone- and muscle-related traits. While Wnt16 is necessary for bone mass and strength, this fails to explain pleiotropy at this locus. Here, we show wnt16 is required for spine and muscle morphogenesis in zebrafish. In embryos, wnt16 is expressed in dermomyotome and developing notochord, and contributes to larval myotome morphology and notochord elongation. Later, wnt16 is expressed at the ventral midline of the notochord sheath, and contributes to spine mineralization and osteoblast recruitment. Morphological changes in wnt16 mutant larvae are mirrored in adults, indicating that wnt16 impacts bone and muscle morphology throughout the lifespan. Finally, we show that wnt16 is a gene of major effect on lean mass at the CPED1-WNT16 locus. Our findings indicate that Wnt16 is secreted in structures adjacent to developing bone (notochord) and muscle (dermomyotome) where it affects the morphogenesis of each tissue, thereby rendering wnt16 expression into dual effects on bone and muscle morphology. This work expands our understanding of wnt16 in musculoskeletal development and supports the potential for variants to act through WNT16 to influence bone and muscle via parallel morphogenetic processes.
