Research ArticleStem Cells

Thy-1 (CD90) promotes bone formation and protects against obesity

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Science Translational Medicine  08 Aug 2018:
Vol. 10, Issue 453, eaao6806
DOI: 10.1126/scitranslmed.aao6806

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Stem cells’ balancing act

Mesenchymal stem cells (MSCs) differentiate into multiple cell types. Picke et al. investigated how MSC differentiation is regulated to maintain homeostasis between the bone and fat lineages. Genetic deletion of Thy-1, a protein expressed on multiple cell types including MSCs, prevented MSC differentiation into osteoblasts but promoted differentiation into adipocytes. Thy-1–deficient mice had increased body fat and decreased bone mass. High-fat diet induced obesity in wild-type mice and concurrent reduction in bone formation, which was associated with decreased Thy-1 expression on MSCs. Obese human subjects and subjects with osteoporosis showed reductions in serum soluble Thy-1. This study suggests that Thy-1 regulates the balance between bone and fat lineages, with possible implications for bone and metabolic disorders.

Abstract

Osteoporosis and obesity result from disturbed osteogenic and adipogenic differentiation and present emerging challenges for our aging society. Because of the regulatory role of Thy-1 in mesenchyme-derived fibroblasts, we investigated the impact of Thy-1 expression on mesenchymal stem cell (MSC) fate between osteogenic and adipogenic differentiation and consequences for bone formation and adipose tissue development in vivo. MSCs from Thy-1–deficient mice have decreased osteoblast differentiation and increased adipogenic differentiation compared to MSCs from wild-type mice. Consistently, Thy-1–deficient mice exhibited decreased bone volume and bone formation rate with elevated cortical porosity, resulting in lower bone strength. In parallel, body weight, subcutaneous/epigonadal fat mass, and bone fat volume were increased. Thy-1 deficiency was accompanied by reduced expression of specific Wnt ligands with simultaneous increase of the Wnt inhibitors sclerostin and dickkopf-1 and an altered responsiveness to Wnt. We demonstrated that disturbed bone remodeling in osteoporosis and dysregulated adipose tissue accumulation in patients with obesity were mirrored by reduced serum Thy-1 concentrations. Our findings provide new insights into the mutual regulation of bone formation and obesity and open new perspectives to monitor and to interfere with the dysregulated balance of adipogenesis and osteogenesis in obesity and osteoporosis.

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