Knockdown of GCNT2 promoted osteoblast differentiation by activating PI3K/AKT/mTOR pathway in osteoblasts.

Osteoporosis (OP) constitutes a systemic bone metabolic disorder characterized by complex pathogenesis and clinical recalcitrance. The regulatory mechanisms underlying OP require further investigation. Microarray profiling was employed to identify abnormally expressed genes in OP patients. OP patients and MC3T3-E1 osteoblasts were utilized for in vivo and in vitro research. Alkaline phosphatase (ALP) staining intensity, alizarin red staining (ARS) intensity, and expression of Runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN) were assessed to evaluate osteoblast differentiation. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to measure mRNA expression, while protein expression was determined by Western blot analysis. Glucosaminyl (N-acetyl) transferase 2 (GCNT2) was upregulated in OP and Dex-treated MC3T3-E1 cells. Dex-treated MC3T3-E1 cells, whose osteogenic differentiation was impaired, served as the OP model. ALP and ARS intensities, together with Runx2, OCN, and OPN expression elevated by GCNT2 knockdown, were attenuated by the PI3K inhibitor LY294002. Suppressed GCNT2 promoted osteoblast differentiation by activating PI3K/AKT/mTOR signaling pathway in OP. These in-vitro findings suggest that GCNT2 knockdown merits further pre-clinical evaluation as a potential therapeutic strategy for OP.