Regulation And Mechanism Of ABCA8 On Osteoblast Senescence

To investigate the role of ATP-binding cassette subfamily A member 8 (ABCA8) in osteoblast senescence and its mechanistic contribution to osteoporosis. Human bone marrow mesenchymal stem cells (hBMSCs) were isolated by enzymatic digestion and validated phenotypically. ABCA8 expression was analyzed via RT-PCR (mRNA) and Western blot (protein). In vivo, C57 mice were subjected to adenovirus-mediated ABCA8 overexpression (OVE) or sham surgery. Femoral bone density and trabecular parameters (thickness, morphology) were quantified using micro-CT. Osteogenic/aging markers were assessed via RT-PCR and immunoblotting. Pre-osteoblast lines with ABCA8 overexpression or knockout were generated to evaluate osteogenic differentiation and senescence (β-galactosidase staining, immunofluorescence). Both RT-PCR and Western blot confirmed the elevated expression of ABCA8 at the mRNA and protein levels, respectively, in aging hBMSCs. The in vivo experiments showed that ABCA8 overexpression led to osteoblast senescence in OVX mice and decreased osteogenic differentiation. The results of in vitro experiments showed that ABCA8 gene knockout increased the osteogenic differentiation ability of hBMSC cells,whereas ABCA8 overexpression reduced osteogenic differentiation. This study reveals, for the first time, the significant regulatory role of ABCA8 in osteoporosis, particularly its key role in osteoblast aging. Furthermore, it clarifies the mechanism through which ABCA8 affects osteoblast differentiation.