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The effect of matrix stiffness on the chondrogenic differentiation of mesenchymal stem cells

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Abstract

Articular cartilage is one of the most important weight-bearing components in human body, thus the chondrogenesis of stem cells is reactive to many intracellular and extracellular mechanical signals. As a unique physical cue, matrix stiffness plays an integral role in commitment of stem cell fate. However, when examining the downstream effects of matrix stiffness, most studies used different soluble factors to assist physical inducing process, which may mask the chondrogenic effects of matrix stiffness. Here we fabricated polyacrylamide (PAAm) hydrogels with gradient stiffness to unravel the role of matrix stiffness in chondrogenic process of mesenchymal stem cells (MSCs), with or without TGF-β3 as induction factor. The results showed that with micromass culture mimicking relatively high cell density in vivo, the chondrogenic differentiation of MSCs can be promoted by soft substrates (about 0.5 kPa) independently with assembled cytoskeleton. Further analysis indicated that addition of TGF-β3 generally increased expression level of cartilage-related markers and masked the stiffness-derived expression pattern of hypertrophic markers. These results demonstrate how mechanical cues experienced in developmental context regulate commitment of stem cell fate and have significant impact on the design of tissue regeneration materials.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

The project was supported by the National Natural Science Foundation of China (31971240).

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Authors and Affiliations

  1. Department of Orthodontics, West China School of Stomatology, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14#, 3rd Section, Renmin South Road, 610041, Chengdu, Sichuan, China

    Yimei Zhou & Juan Li

  2. Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China

    Jingyi Qiu

  3. Department of Preventive Dentistry, West China School of Stomatology, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14#, 3rd Section, Renmin South Road, 610041, Chengdu, Sichuan, China

    Lingyun Wan

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  1. Yimei Zhou
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  2. Jingyi Qiu
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  4. Juan Li
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Contributions

All authors contributed to the study conception and design. Juan Li and Jingyi Qiu designed the experiments. Jingyi Qiu and Lingyun Wan performed the experiments. Yimei Zhou and Jingyi Qiu analyzed the experimental results. Yimei Zhou and Lingyun Wan wrote the manuscript with help from all authors. All authors read and approved the final manuscript.

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Correspondence to Juan Li.

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Zhou, Y., Qiu, J., Wan, L. et al. The effect of matrix stiffness on the chondrogenic differentiation of mesenchymal stem cells. J Mol Histol 53, 805–816 (2022). https://doi.org/10.1007/s10735-022-10094-6

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