TY  - JOUR
A1  - Schanbacher, Constanze
A1  - Bieber, Michael
A1  - Reinders, Yvonne
A1  - Cherpokova, Deya
A1  - Teichert, Christina
A1  - Nieswandt, Bernhard
A1  - Sickmann, Albert
A1  - Kleinschnitz, Christoph
A1  - Langhauser, Friederike
A1  - Lorenz, Kristina
T1  - ERK1/2 activity is critical for the outcome of ischemic stroke
JF  - International Journal of Molecular Sciences
N2  - Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2\(^{wt}\)) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood–brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIP\(^{wt}\)) and its phosphorylation-deficient mutant RKIP\(^{S153A}\), known inhibitors of the ERK1/2 signaling cascade. RKIP\(^{wt}\) and RKIP\(^{S153A}\) attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke.
KW  - ERK1/2
KW  - tMCAO
KW  - ischemic stroke
KW  - RKIP
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283991
SN  - 1422-0067
VL  - 23
IS  - 2
ER  - 
TY  - JOUR
A1  - Wang, Chenglong
A1  - Stöckl, Sabine
A1  - Li, Shushan
A1  - Herrmann, Marietta
A1  - Lukas, Christoph
A1  - Reinders, Yvonne
A1  - Sickmann, Albert
A1  - Grässel, Susanne
T1  - Effects of extracellular vesicles from osteogenic differentiated human BMSCs on osteogenic and adipogenic differentiation capacity of naïve human BMSCs
JF  - Cells
N2  - 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.
KW  - extracellular vesicles
KW  - mesenchymal stem cells
KW  - osteogenic potential
KW  - osteogenic differentiation
KW  - adipogenic differentiation
KW  - ECM remodeling
KW  - bone regeneration
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286112
SN  - 2073-4409
VL  - 11
IS  - 16
ER  -