Current treatment strategies for osteoporosis are ineffective at reversing the characteristic bone tissue abnormalities associated with increased fragility. Now, new research reports that THY1 membrane glycoprotein is important for osteogenesis promoted by mesenchymal stem cell (MSC) differentiation.

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MSCs are thought to have a central role in the development of osteoporosis. Patients with osteoporosis have dramatic bone loss, while bone marrow adiposity is increased — this is caused by an imbalance between osteogenic and adipogenic MSC differentiation. “Studies have shown that THY1, which is expressed on the surface of MSCs, has a regulatory role in mesenchyme-derived fibroblast differentiation,” explains corresponding author Anja Saalbach “Therefore, in the present study, we investigated the effect of THY1 expression on the fate of MSCs, with a focus on osteogenic and adipogenic differentiation.”

To investigate the effect of THY1 on the balance between osteogenesis and adipogenesis in bone marrow, the authors used micro-computed tomography, histology and biomechanical tests to analyse bone of THY1-deficient and wild-type mice. Samples from these mice were also taken and analysed in vitro. Saalbach and colleagues also measured levels of THY1 in the serum of healthy humans and humans who had disturbed bone formation or obesity.

“We identified THY1 as a critical molecule for MSC differentiation promoting bone formation, while inhibiting adipogenesis and obesity,” adds Saalbach. “Furthermore, THY1 levels in the serum indicated that disturbed bone remodelling in osteoporosis or dysregulated adipose tissue accumulation in patients with obesity are mirrored by reduced serum concentrations of THY1”.

We identified THY1 as a critical molecule for MSC differentiation promoting bone formation signalling

Saalbach writes that future studies should focus on further understanding how THY1 mediates bone mass and concurrently negatively regulates adipose tissue. Targeting the balance between osteogenesis and adipogenesis could be an attractive strategy for novel therapies against osteoporosis.