Nejvíce citovaný článek - PubMed ID 10022972
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