MSCs, with the potential for multidirectional differentiation into chondrocytes, osteoblasts, and adipocytes, play a pivotal role in the maintenance of bone-lipid balance and serve as critical targets for treating diseases related to bone-lipid metabolism, such as osteoporosis, diabetes, and obesity (James, 2013). Diabetes can induce adipogenic differentiation of MSCs, leading to the accumulation of fat in the bone marrow cavity, liver, and other areas, accompanied by chronic inflammation (Lee et al., 2022). This, in turn, increases the risk of fractures, liver fibrosis, sclerosis, and cardiovascular diseases, posing a severe threat to the overall health of diabetic patients (Ferland-McCollough et al., 2018). In the typical manifestation of age-related osteoporosis, MSCs exhibit a diminished capacity for osteogenic differentiation and an enhanced capacity for adipogenic differentiation (Jiang et al., 2021). This imbalance results in bone loss, marrow fat accumulation, and the development of serious complications such as back pain, kyphosis, and even fractures (Pignolo et al., 2021). The regulation of MSCs osteogenic and adipogenic differentiation involves complex interactions among various factors, including hormones, transcription factors, and cytokines (Almalki and Agrawal, 2016). Among these, transcription factors play a particularly important role, as differences in these factors under different physiological conditions can lead to changes in bone-lipid balance and the occurrence of related diseases (Almalki and Agrawal, 2016).

ZFPs are a vital group of transcription factors. Recent research has revealed the crucial roles played by these factors in maintaining the delicate equilibrium between bone and fat metabolism, migration and invasion of cancer cells, occurrence of neurodegenerative diseases, regulation of the cell cycle, and other biological processes (Sobocinska et al., 2021, Loh et al., 2020, Kong et al., 2023, Liu et al., 2023, Le et al., 2021a). In this review, we will comprehensively summarize how ZFPs influence the osteogenic and adipogenic differentiation of MSCs through different signaling pathways, transcription factors, and epigenetic mechanisms. Furthermore, we will outline the regulatory mechanisms of ZFPs in controlling osteogenic and adipogenic differentiation based on various stages of MSC differentiation.