RETRACTED ARTICLE: Saxagliptin enhances osteogenic differentiation in MC3T3-E1 cells, dependent on the activation of AMP-activated protein kinase α (AMPKα)/runt-related transcription factor-2 (Runx-2)

Abstract

Osteoporosis is a metabolic bone disease commonly observed in the elderly, and its pathogenesis is associated with declined osteogenic differentiation. Osteogenic differentiation could be facilitated by the activation of the AMP-activated protein kinase (AMPK) pathway. Saxagliptin, an anti-diabetic agent with inhibitory effects against dipeptidyl peptidase 4 (DPP-4), has been recently reported to induce the activation of the AMPK pathway. The present study proposes to explore the function and mechanism of Saxagliptin in osteogenic differentiation. Osteogenic differentiation induction medium (ODIM) was utilized to induce osteogenic differentiation in MC3T3-E1 cells. Significantly increased mineral nodule formation, elevated alkaline phosphatase (ALP) activity, and upregulated expression of osteogenic marker genes activating transcription factor-4 (ATF-4), osteopontin (OPN), and type I collagen (Col1) were observed in ODIM-cultured MC3T3-E1 cells, all of which were further enhanced by the introduction of Saxagliptin. The elevated expression level of runt-related transcription factor-2 (Runx-2), an important transcriptional factor involved in the progression of osteogenic differentiation, in ODIM-cultured MC3T3-E1 cells was further promoted by Saxagliptin. The AMPK pathway in ODIM-cultured MC3T3-E1 cells was significantly activated by Saxagliptin, and the functions of Saxagliptin in promoting osteogenic differentiation were abolished by compound C, the inhibitor of the AMPK pathway. Conclusively, Saxagliptin enhanced osteogenic differentiation in MC3T3-E1 cells, dependent on the activation of AMPKα/RUNX-2.

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“…OPN is an osteogenic marker of osteoblast mineralization and maturation. In addition, OCN is identified as an osteogenic marker of terminal stage in osteoblasts. − …”

“…In addition, the graphene has a large specific surface area and there are some wrinkles and ripples on the surface of graphene, which could sustain lateral stresses that might affect cytoskeletal tension. , This leads to changes in cytoskeletal organization/structure and induces cell differentiation . Obtained by SPS, composite particles have a strong noncovalent binding capacity and act as preconcentrators for chemicals, resulting in proteins and growth factors accumulate on their surface for osteogenic inducers, accelerating the differentiation progression of MSCs to the osteogenic lineage . The surface of GNPs flakes in the particles obtained by ultrasound treatment was mostly covered by ECPP particles and therefore could not absorb the molecules directly.…”

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Exosomes: A novel insight into traditional Chinese medicine

“…AMP-activated protein kinase (AMPK) regulates the differentiation of osteoblasts and bone formation ( Li et al, 2018 ). It has been demonstrated that the activation of the AMPK/Runx2 pathway is an important mechanism underlying the facilitating effects of agents against osteogenic differentiation in MC3T3-E1 cells ( Wang Q. et al, 2022 ). Thus, whether Exo-Ica enhances osteogenic differentiation in MC3T3-E1 cells by regulating the AMPK-α/Runx2 pathway may be an interesting direction in the next studies.…”