The study aimed to investigate the influence of obesity on cellular features of equine endometrial progenitor cells (Eca EPCs), including viability, proliferation capacity, mitochondrial metabolism, and oxidative homeostasis. Eca EPCs derived from non-obese (non-OB) and obese (OB) mares were characterized by cellular phenotype and multipotency. Obesity-induced changes in the activity of Eca EPCs include the decline of their proliferative activity, clonogenic potential, mitochondrial metabolism, and enhanced oxidative stress. Eca EPCs isolated from obese mares were characterized by an increased occurrence of early apoptosis, loss of mitochondrial dynamics, and senescence-associated phenotype. Attenuated metabolism of Eca EPCs OB was related to increased expression of pro-apoptotic markers (CASP9, BAX, P53, P21), enhanced expression of OPN, PI3K, and AKT, simultaneously with decreased signaling stabilizing cellular homeostasis (including mitofusin, SIRT1, FOXP3). Obesity alters functional features and the self-renewal potential of endometrial progenitor cells. The impaired cytophysiology of progenitor cells from obese endometrium predicts lower regenerative capacity if used as autologous transplants.

• Klíčová slova
• cellular metabolism, endometrial progenitor cells, obesity, self-renewal potential,
• MeSH
• endometrium metabolismus   MeSH
• endoteliální progenitorové buňky * metabolismus   MeSH
• fenotyp MeSH
• kmenové buňky metabolismus   MeSH
• koně MeSH
• obezita metabolismus   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts' differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

• Klíčová slova
• differentiation, miR-21-5p, osteoblasts, osteoclasts, osteogenesis, precursor cells,
• MeSH
• buněčná diferenciace genetika   MeSH
• buněčné linie MeSH
• extracelulární matrix metabolismus   MeSH
• kokultivační techniky MeSH
• kyselá fosfatasa rezistentní k tartarátu metabolismus   MeSH
• messenger RNA genetika   MeSH
• mikro RNA genetika   metabolismus   MeSH
• myši MeSH
• osteoblasty metabolismus   MeSH
• osteogeneze genetika   MeSH
• osteoklasty metabolismus   MeSH
• osteopontin genetika   metabolismus   MeSH
• parakrinní signalizace genetika   MeSH
• protein PEBP2alfaA genetika   metabolismus   MeSH
• resorpce kosti metabolismus   MeSH
• signální transdukce genetika   MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Acp5 protein, mouse MeSH Prohlížeč
• kyselá fosfatasa rezistentní k tartarátu MeSH
• messenger RNA MeSH
• mikro RNA MeSH
• MIRN21 microRNA, mouse MeSH Prohlížeč
• osteopontin MeSH
• protein PEBP2alfaA MeSH
• Runx2 protein, mouse MeSH Prohlížeč
• Spp1 protein, mouse MeSH Prohlížeč