Protein phosphorylation, osteoblasts and the link with BMD variation

PhosSNPs are single nucleotide polymorphisms (SNPs) that impact on the phosphorylation of proteins. Here, Deng et al. performed a small genome-wide association study in three population samples to look for phosSNPs associated with bone mineral density (BMD).1

The researchers used samples from 5 000 unrelated individuals, identifying and replicating three phosSNPs associated with BMD at the spine and hip in Caucasians. One of these phosSNPs—rs6265—was within the BDNF gene (which encodes brain-derived neurotrophic factor) in samples from Chinese individuals. People from both ethnic backgrounds who were homozygous for the minor allele of BDNF had significantly lower BMD scores at the hip compared to heterozygotes and those homozygous for the major BDNF allele.

In vitro experiments were done to discover the effect of transfecting osteoblastic cells with either wild-type BDNF or BDNF with the minor allele at rs6265. The results demonstrated that transfection with the variant BDNF reduced protein phosphorylation of BDNF at amino acid T62. This reduced expression of three osteoblastic genes – encoding bone morphogenetic protein 2, alkaline phosphatase and osteopontin – and decreased osteoblastic activity significantly.

Editor's comment: We already know that BDNF is important for chondrocyte and osteoblast function, ossification, cartilage development, bone growth, development and remodeling, and osteogenesis. This study highlights the impact of BDNF variants on BMD in various human populations. It is interesting that this same gene has also shown an association with body mass index variation and age at menarche.