Outpatient Department of Oral and Maxillofacial Surgery, School of Stomatology, Capital Medical University, Beijing, 100050, China.
Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, 100050, China.
Adv Biol (Weinh). 2024 May;8(5):e2300642. doi: 10.1002/adbi.202300642. Epub 2024 Mar 28.
Senescent pre-osteoblasts have a reduced ability to differentiate, which leads to a reduction in bone formation. It is critical to identify the keys that regulate the differentiation fate of senescent pre-osteoblasts. LINC01013 has an essential role in cell stemness, differentiation, and senescence regulation. This study aims to examine the role and mechanism of LINC01013 in regulating osteogenic differentiation in senescent human embryonic osteoblast cell line (hFOB1.19) cells induced by hydrogen peroxide (HO). The results show that LINC01013 decreased alkaline phosphatase activity, mineralization of hFOB1.19 cells in vitro, and the expression of collagen II, osteocalcin, and bone sialoprotein. LINC01013 knockdown enhances the osteogenesis of hFOB1.19 cells and rescues osteogenic differentiation impaired by HO. METTL3 negatively regulates LINC01013 expression, enhancing hFOB1.19 cells' osteogenesis in vitro and in vivo. METTL3 overexpression can enhance hFOB1.19 cells' osteogenic differentiation impaired by HO. YTHDF2 promotes LINC01013 decay, facilitating osteogenic differentiation. YTHDF2 overexpression rescues hFOB1.19 cells osteogenic differentiation impaired by HO. Taken together, METTL3 upregulates osteogenic differentiation by inhibiting LINC01013, and YTHDF2 accelerates LINC01013 degradation, reducing its inhibitory effect. This study highlights LINC01013 as a key regulator in the fate switching process of senescent hFOB1.19 cells, impacting osteogenic differentiation.
衰老的前成骨细胞分化能力降低，导致骨形成减少。确定调节衰老前成骨细胞分化命运的关键因素至关重要。LINC01013 在细胞干性、分化和衰老调控中起着重要作用。本研究旨在探讨 LINC01013 在过氧化氢（HO）诱导的衰老人胚胎成骨细胞系（hFOB1.19）细胞中调节成骨分化中的作用及其机制。结果表明，LINC01013 降低了碱性磷酸酶活性、hFOB1.19 细胞的体外矿化以及胶原蛋白 II、骨钙素和骨涎蛋白的表达。LINC01013 敲低增强了 hFOB1.19 细胞的成骨作用，并挽救了 HO 引起的成骨分化受损。METTL3 负调控 LINC01013 的表达，增强 hFOB1.19 细胞体外和体内的成骨作用。METTL3 过表达可增强 HO 引起的 hFOB1.19 细胞成骨分化受损。YTHDF2 促进 LINC01013 衰减，促进成骨分化。YTHDF2 过表达可挽救 HO 引起的 hFOB1.19 细胞成骨分化受损。总之，METTL3 通过抑制 LINC01013 上调成骨分化，而 YTHDF2 加速 LINC01013 降解，降低其抑制作用。本研究强调了 LINC01013 作为衰老 hFOB1.19 细胞命运转换过程中的关键调节因子，影响成骨分化。
