Department of Medicine, University of Verona and Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy.
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 10, 37100, Verona, Italy.
Stem Cell Res Ther. 2021 Jun 5;12(1):326. doi: 10.1186/s13287-021-02396-5.
Methylsulfonylmethane (MSM) is a nutraceutical compound which has been indicated to counteract osteoarthritis, a cartilage degenerative disorder. In addition, MSM has also been shown to increase osteoblast differentiation. So far, few studies have investigated MSM role in the differentiation of mesenchymal stem cells (MSCs), and no study has been performed to evaluate its overall effects on both osteogenic and chondrogenic differentiation. These two mutually regulated processes share the same progenitor cells.
Therefore, with the aim to evaluate the effects of MSM on chondrogenesis and osteogenesis, we analyzed the expression of SOX9, RUNX2, and SP7 transcription factors in vitro (mesenchymal stem cells and chondrocytes cell lines) and in vivo (zebrafish model). Real-time PCR as well Western blotting, immunofluorescence, and specific in vitro and in vivo staining have been performed. Student's paired t test was used to compare the variation between the groups.
Our data demonstrated that MSM modulates the expression of differentiation-related genes both in vitro and in vivo. The increased SOX9 expression suggests that MSM promotes chondrogenesis in treated samples. In addition, RUNX2 expression was not particularly affected by MSM while SP7 expression increased in all MSM samples/model analyzed. As SP7 is required for the final commitment of progenitors to preosteoblasts, our data suggest a role of MSM in promoting preosteoblast formation. In addition, we observed a reduced expression of the osteoclast-surface receptor RANK in larvae and in scales as well as a reduced pERK/ERK ratio in fin and scale of MSM treated zebrafish.
In conclusion, our study provides new insights into MSM mode of action and suggests that MSM is a useful tool to counteract skeletal degenerative diseases by targeting MSC commitment and differentiation.
甲磺酰甲烷(MSM)是一种营养补充剂化合物,已被证明可对抗骨关节炎,这是一种软骨退行性疾病。此外,MSM 还已被证明可增加成骨细胞分化。到目前为止,很少有研究调查 MSM 在间充质干细胞(MSCs)分化中的作用,也没有研究评估其对成骨和软骨分化的整体影响。这两个相互调节的过程共享相同的祖细胞。
因此,为了评估 MSM 对软骨形成和成骨的影响,我们在体外(间充质干细胞和软骨细胞系)和体内(斑马鱼模型)分析了 SOX9、RUNX2 和 SP7 转录因子的表达。进行了实时 PCR 以及 Western blot、免疫荧光和特定的体外和体内染色。使用学生配对 t 检验比较组间的变化。
我们的数据表明,MSM 在体外和体内调节分化相关基因的表达。SOX9 表达的增加表明 MSM 促进了处理样本中的软骨形成。此外,MSM 对 RUNX2 表达的影响不大,而 SP7 表达在所有分析的 MSM 样本/模型中均增加。由于 SP7 是祖细胞最终向成骨前体细胞分化所必需的,我们的数据表明 MSM 在促进成骨前体细胞形成中起作用。此外,我们观察到幼虫和鳞片中破骨细胞表面受体 RANK 的表达减少,以及 MSM 处理的斑马鱼鳍和鳞片中 pERK/ERK 比值降低。
总之,我们的研究提供了 MSM 作用模式的新见解,并表明 MSM 是通过靶向 MSC 分化来对抗骨骼退行性疾病的有用工具。