Diabetes mellitus (DM) is a heterogeneous metabolic disease characterised by elevated blood glucose [1]. The number of patients with DM has increased rapidly in the past few decades [2]. DM causes bone tissue-related complications, such as an increased risk of fracture and slow bone healing [3,4]. Such complications are caused by a decrease in mineral density, abnormal microstructure, and weakened osteogenic function due to the high-glucose conditions [5].

Bone marrow-derived mesenchymal stem cells (BMSCs) are pluripotent stem cells that are vital in bone regeneration and bone metabolism balance [6,7]. A high-glucose environment caused by diabetes can inhibit BMSC proliferation, migration, and osteogenic differentiation [8,9]. In this context, the reactive oxygen species (ROS) production also increases, leading to oxidative stress, which in turn accelerates BMSC senescence [10,11]. Therefore, hyperglycaemia is an inevitable barrier to stem cell-mediated regeneration [12].

Phytic acid (PA, molecular formula: C6HOP6) is an organic phosphoric acid with multiple bioactivities, such as anti-diabetic, anti-cancer, and anti-inflammatory activities [13,14]. Furthermore, PA is biocompatible [15] and is typically used in surface modification as a chelating agent to improve the properties of materials and to induce BMSC proliferation and osteogenic differentiation [16]. However, few studies have examined the effects and molecular mechanisms of PA on BMSCs exposed to high-glucose levels.

Mitogen-activated protein kinase (MAPK) is a superfamily comprising kinases that regulate the cell physiological status through phosphorylation. The most widely studied MAPKs are the c-Jun N-terminal kinase (JNK), extracellular regulated protein kinase (ERK), and P38 signalling pathways [17]. The MAPK signalling pathway plays a pivotal role in regulating the physiological activities of BMSCs. Activation of the MAPK pathway can promote BMSC osteogenic differentiation in diabetic mice [18,19]. Furthermore, the ERK pathway inhibits the increase of ROS and prevents BMSC senescence [20].

Hence, the present study aimed to investigate whether PA attenuates the repression of osteogenic differentiation and cell senescence of BMSCs in the high-glucose environment, exploring the potential underlying mechanisms.