Original Research ARTICLE
Thy-1 deficiency augments bone loss in obesity by affecting bone formation and resorption
- 1Abteilung für Endokrinologie, Diabetes und Knochenkrankheiten, Medizinische Klinik und Poliklinik III, Technische Universität Dresden, Germany
- 2Institut für Vergleichende Molekulare Endokrinologie, Universität Ulm, Germany
- 3Institut für Biomechanik, TUHH Technische Universität Hamburg, Germany
- 4Department of Osteology and Biomechanics, University Medical Center, Germany
- 5Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikums Leipzig, Germany
Accumulation of adipose tissue in obesity was reported to be both protective and deleterious to bone health. Recently, Thy-1 was discovered to stimulate osteogenic differentiation of mesenchymal stem cells while it concurrently reduces adipogenic differentiation. Therefore, Thy-1 positively regulates bone mass and strength. We aimed to obtain mechanistic insights into how increased fat accumulation negatively affects bone mass and bone formation. Therefore, we investigated the impact of Thy-1 on bone metabolism under 12-weeks high fat diet (HFD)-induced obese conditions by µCT, histological analysis and Fourier-transform infrared spectroscopy (FTIR).
Indeed, mice lacking Thy-1 showed increased body fat mass after HFD compared to WT mice. In parallel, obese Thy-1-deficient mice displayed a reduced trabecular bone volume (-38%) and bone formation (-57%). FTIR analysis showed that the mineral-to-matrix ratio decreased (-8%) and the carbonate-to-phosphate ratio increased (+5%) indicating changes in collagen amount and mineral age, respectively. In contrast to lean mice, under obese conditions, lack of Thy-1 affected both osteoblast and osteoclast function. Elevated numbers of osteoclasts (+39%), increased expression of tartrate-resistance acid phosphatase (+86%), and higher serum levels of collagen type 1 cross-linked N-telopeptide (+30%) in obese Thy-1-deficient mice indicated that Thy-1 promotes osteoclast activity under obese conditions. Analysis of bone marrow fat revealed a dramatic increase (+56%) associated with strongly upregulated tumor necrosis factor α expression (+46%) in Thy-1-deficient compared to obese WT mice.
In summary, our findings show that in obesity lack of Thy-1 results in a reduced bone mass due to an increased adipogenic and decreased osteogenic differentiation as well as by concurrently increased osteoclast differentiation. Increased TNFα expression caused by an amplified fat tissue accumulation might be responsible for elevated osteoclast activity in obese Thy-1-deficient mice.
Keywords: Thy-1 (CD90), bone mass, osteoblast, osteoclast, Adipocyte, differentiation, TNF - α
Received: 27 Jun 2018;
Accepted: 13 Sep 2018.
Edited by:Emanuela Felley-Bosco, Universität Zürich, Switzerland
Reviewed by:Zhizhan Gu, Dana–Farber Cancer Institute, United States
David Lutz, Abteilung für Neuroanatomie und Molekulare Hirnforschung, Ruhr-Universität Bochum, Germany
Copyright: © 2018 Picke, Campbell, Schmidt, Busse, Rauner, Simon, Anderegg, Hofbauer and Saalbach. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Anja Saalbach, Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikums Leipzig, Leipzig, Germany, firstname.lastname@example.org