BoneKEy Reports | BoneKEy Watch

Novel genes identified that could regulate height


Adult height may be influenced by 180 loci already identified by a meta-analysis of genome-wide association studies (GWAS), but it is far from clear which genes within these loci act directly on bone growth. By performing expression microarray studies of the growth plate from rats and mice, Lui et al. sought the causative genes within these loci that function within the growth plate to modify bone elongation.

The authors stress that their method allows even single genes involved in height determination to be identified, not just overall loci and not just genes already known to act within well-known molecular pathways. A total of 78 genes were implicated as playing a role in growth plate function, including multiple genes that participate in PTHrP-IHH, BMP and CNP signaling.

Novel genes not previously associated with the growth plate included RSPO3, which activates Wnt5a signaling, known to be important in growth plate chondrocyte proliferation and differentiation. This gene was recently associated with bone mineral density in GWAS.

Editor’s comment: The discovery of RSPO3 and other novel genes implicated in growth plate chondrogenesis should now enable further studies involving knockout mice that can be used in mechanistic studies. These should uncover more about the molecular pathways through which these genes act, and will enable further exploration of their relationship to human growth regulation.

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