Effects of Extracellular Vesicles from Osteogenic Differentiated Human BMSCs on Osteogenic and Adipogenic Differentiation Capacity of Naïve Human BMSCs

Chenglong Wang; Sabine Stöckl; Shushan Li; Marietta Herrmann; Christoph Lukas; Yvonne Reinders; Albert Sickmann; Susanne Grässel

doi:10.3390/cells11162491

Effects of Extracellular Vesicles from Osteogenic Differentiated Human BMSCs on Osteogenic and Adipogenic Differentiation Capacity of Naïve Human BMSCs

Cells. 2022 Aug 11;11(16):2491. doi: 10.3390/cells11162491.

Authors

Chenglong Wang¹, Sabine Stöckl¹, Shushan Li¹, Marietta Herrmann², Christoph Lukas¹, Yvonne Reinders³, Albert Sickmann^{3

4

5}, Susanne Grässel¹

Affiliations

¹ Department of Orthopedic Surgery, Experimental Orthopedics, Centre for Medical Biotechnology (ZMB), University of Regensburg, 93053 Regensburg, Germany.
² IZKF Group Tissue Reg. in Musculoskeletal Dis., University Hospital & Bernhard-Heine-Centrum for Locomotion Res., University of Würzburg, 97070 Würzburg, Germany.
³ Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., Bunsen-Kirchhoff-Straße 11, 44139 Dortmund, Germany.
⁴ Medizinisches Proteom-Center, Ruhr-Universität Bochum, 44801 Bochum, Germany.
⁵ Department of Chemistry, College of Physical Sciences, University of Aberdeen, Aberdeen AB24 3FX, UK.

Abstract

Osteoporosis, or steroid-induced osteonecrosis of the hip, is accompanied by increased bone marrow adipogenesis. Such a disorder of adipogenic/osteogenic differentiation, affecting bone-marrow-derived mesenchymal stem cells (BMSCs), contributes to bone loss during aging. Here, we investigated the effects of extracellular vesicles (EVs) isolated from human (h)BMSCs during different stages of osteogenic differentiation on the osteogenic and adipogenic differentiation capacity of naïve (undifferentiated) hBMSCs. We observed that all EV groups increased viability and proliferation capacity and suppressed the apoptosis of naïve hBMSCs. In particular, EVs derived from hBMSCs at late-stage osteogenic differentiation promoted the osteogenic potential of naïve hBMSCs more effectively than EVs derived from naïve hBMSCs (naïve EVs), as indicated by the increased gene expression of COL1A1 and OPN. In contrast, the adipogenic differentiation capacity of naïve hBMSCs was inhibited by treatment with EVs from osteogenic differentiated hBMSCs. Proteomic analysis revealed that osteogenic EVs and naïve EVs contained distinct protein profiles, with pro-osteogenic and anti-adipogenic proteins encapsulated in osteogenic EVs. We speculate that osteogenic EVs could serve as an intercellular communication system between bone- and bone-marrow adipose tissue, for transporting osteogenic factors and thus favoring pro-osteogenic processes. Our data may support the theory of an endocrine circuit with the skeleton functioning as a ductless gland.

Keywords: ECM remodeling; adipogenic differentiation; bone regeneration; extracellular vesicles; mesenchymal stem cells; osteogenic differentiation; osteogenic potential.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipogenesis
Cell Differentiation
Extracellular Vesicles*
Humans
Osteogenesis*
Proteomics

Grants and funding

This work was funded by a grant of the German Society of Orthopedics and Orthopedic Surgery (DGOOC) to S.G. and M.H. Y.R. and A.S. acknowledge the support from the “Ministerium für Kultur und Wissenschaft des Landes Nordrhein-Westfalen” and “Der Regierende Bürgermeister von Berlin, Senatskanzlei Wissenschaft und Forschung”. Additionally, Y.R. and A.S. acknowledge funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—project identifier: 236177352 (SFB1116/TPS01).