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Hexavalent Chromium Induces Cartilage Degeneration and Osteoarthritis Pathogenesis

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Abstract

Hexavalent chromium (Cr(VI)), an environmental hazard, can damage human organs and is associated with various diseases when ingested; however, its effects on the progression of osteoarthritis, the most prevalent form of arthritis, remain unknown. Therefore, we investigate the effects of Cr(VI) on osteoarthritis pathogenesis by evaluating the mechanistic role of a novel Cr(VI) “hot spot,” articular cartilage, using a noncarcinogenic concentration of Cr(VI) in a murine model. Intra-articular injection of 100 ppm of Cr(VI) resulted in significant cartilage degeneration; mice with surgical destabilization of the medial meniscus exposed to a low oral dose of Cr(VI) for 16 weeks also showed increased osteoarthritis parameters. Immunohistochemical analysis revealed that Cr(VI) increased osteoarthritis induc

ers, including Hif-2α and Zip8, as well as metalloproteinases Mmp3 and Mmp13. Moreover, Cr(VI)-induced Hif-2α and Zip8 promoted Mmp3 and Mmp13 expression through the NF-κB signaling pathway. Collectively, our findings suggest that Cr(VI) can influence articular cartilage degeneration and affect osteoarthritis development through the NF–κB–Hif-2α/Zip8 signaling pathway.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Editage (www.editage.co.kr) for English language editing.

Funding

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (Grant No. 2020R1A2C2004128), and the Basic Science Research Program to Research Institute for Basic Sciences (RIBS) of Jeju National University through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Grant No. 2019R1A6A1A10072987).

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Authors and Affiliations

  1. Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju-si, 63243, Republic of Korea

    Godagama Gamaarachchige Dinesh Suminda, Yunhui Min, Mangeun Kim & Young-Ok Son

  2. Department of Animal Biotechnology, Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju-si, 63243, Republic of Korea

    Yunji Heo, Kyoungtag Do & Young-Ok Son

  3. Bio-Health Materials Core-Facility Center, Jeju National University, Jeju-si, 63243, Republic of Korea

    Young-Ok Son

  4. Practical Translational Research Center, Jeju National University, Jeju-si, 63243, Republic of Korea

    Young-Ok Son

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  1. Godagama Gamaarachchige Dinesh Suminda
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Contributions

GGDS: Conceptualization, Data acquisition, Formal analysis, Roles/Writing-original draft, Writing-review & editing; YM, YH, MK, KD: Data acquisition, Formal analysis, and manuscript approval; Y-OS: Conceptualization, Funding acquisition, Formal analysis, Roles/Writing-original draft, Writing-review & editing. Y-OS: assume all responsibility for the integrity of this work.

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Correspondence to Young-Ok Son.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Jeju National University Animal Care and Use Committee (2022–0025).

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Suminda, G.G.D., Min, Y., Kim, M. et al. Hexavalent Chromium Induces Cartilage Degeneration and Osteoarthritis Pathogenesis. Expo Health 15, 439–453 (2023). https://doi.org/10.1007/s12403-022-00502-3

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