The angiotensin-converting enzyme 2 (ACE2) receptor has been identified as the cell entry point for SARS-CoV-2. Although ACE2 receptors are present in the bone marrow, the effects of SARS-CoV-2 on the biological activity of bone tissue have not yet been elucidated. In the present study we sought to investigate the impact of SARS-CoV-2 on osteoblastic activity in the context of fracture healing. MicroRNA-4485 (miR-4485), which we found to be upregulated in COVID-19 patients, negatively regulates osteogenic differentiation. We demonstrate this effect both in vitro and in vivo . Moreover, we identified the toll-like receptor 4 (TLR-4) as the potential target gene of miR-4485, and showed that reduction of TLR-4 induced by miR-4485 suppresses osteoblastic differentiation in vitro . Taken together, our findings highlight that up-regulation of miR-4485 is responsible for the suppression of osteogenic differentiation in COVID-19 patients, and TLR-4 is the potential target through which miR-4485 acts, providing a promising target for pro-fracture-healing and anti-osteoporosis therapy in COVID-19 patients.
【저자키워드】 SARS-CoV-2, Fracture, differentiation, miR-4485, Osteoblast, 【초록키워드】 ACE2, therapy, ACE2 receptor, in vitro, angiotensin-converting enzyme 2, Bone marrow, toll-like receptor 4, receptor, in vivo, COVID-19 patients, regulate, target gene, reduction, tissue, cell entry, biological activity, Effect, highlight, responsible, upregulated, suppresse, 【제목키워드】 healing, Osteogenic,