The role of Tcf7l2 on bone metabolism

Kailey, Ajai (2023). The role of Tcf7l2 on bone metabolism. University of Birmingham. M.Sc.

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Abstract

People living with Type 2 Diabetes, especially post-menopausal women, have been found to be associated with having a greater risk of developing bone fractures. The single nucleotide polymorphism (SNP) rs7903146 for Transcription Factor 7-like 2 (Tcf7l2), characterized by a C to T nucleotide substitution within intron 4 of Tcf7l2, has been found to have the greatest association with T In an earlier study looking at the role of Tcf7l2 on adipose tissue function, we found that adipocyte-specific Tcf7l2 knockout mice had altered plasma osteocalcin content, indicating a potential defect in osteoblast function. The aim of this investigation was to identify whether adipocyte-specific knockout of TCF7L2 loss of bone cell number and bone cell mass. I also aimed to identify whether the Tcf7l2 rs7903146 SNP resulted in impaired human osteoblast function. I found that average osteoblast area was significantly greater within homozygous adipocyte-specific Tcf7l2 knockout mice compared to heterozygous adipocyte-specific Tcf7l2 knockout mice, when fed a NC diet. Preliminary data from human osteoblast cultures suggests homozygote carriers of the rs7903146 SNP have reduced median expression of the bone formation marker Osteocalcin. However, homozygous carriers of the rs7903146 SNP had greater secretion of uncarboxylated and carboxylated Osteocalcin a heterozygous carrier of the rs7903146 SNP. However, more work is needed to confirm these preliminary results. This investigation can be used as a starting point to determine the influence of the Tcf7l2 rs7903146 SNP on osteoblast function and adipocyte specific knockout of Tcf7l2 on osteoblast and osteoclast function, potentially linking Tcf7l2 with T2D associated osteoporosis.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):