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. 2023 Mar 30:11:1171360.
doi: 10.3389/fbioe.2023.1171360. eCollection 2023.

Fullerenol inhibits tendinopathy by alleviating inflammation

Xin Jiao  1   2 , Zengguang Wang  1   2 , Yiming Li  1   2 , Tianchang Wang  1   2 , Chen Xu  1   2 , Xianhao Zhou  1   2 , Yaokai Gan  1   2
Affiliations

Fullerenol inhibits tendinopathy by alleviating inflammation

Xin Jiao et al. Front Bioeng Biotechnol. .

Abstract

Tendinopathy is a common disease in orthopaedics, seriously affecting tendon functions. However, the effects of non-surgical treatment on tendinopathy are not satisfactory and surgical treatments possibly impair the function of tendons. Biomaterial fullerenol has been proved to show good anti-inflammatory effects on various inflammatory diseases. For in vitro experiments, primary rat tendon cells (TCs) were treated by interleukin-1 beta (IL-1β) combined with aqueous fullerenol (5, 1, 0.3 μg/mL). Then inflammatory factors, tendon-related markers, migration and signaling pathways were detected. For in vivo experiments, rat tendinopathy model was constructed by local injection of collagenase into Achilles tendons of rats and fullerenol (0.5, 1 mg/mL) was locally injected 7 days after collagenase injection. Inflammatory factors and tendon-related markers were also investigated. Fullerenol with good water-solubility showed excellent biocompatibility with TCs. Fullerenol could increase expression of tendon-related factors (Collagen I and tenascin C) and decrease expression of inflammatory factors (matrix metalloproteinases-3, MMP-3, and MMP-13) and reactive oxygen species (ROS) level. Simultaneously, fullerenol slowed the migration of TCs and inhibited activation of Mitogen-activated protein kinase (MAPK) signaling pathway. Fullerenol also attenuated tendinopathy in vivo, including reduction of fiber disorders, decrease of inflammatory factors and increase of tendon markers. In summary, fullerenol is a promising biomaterial that can be used to treat tendinopathy.

Keywords: MAPK; ROS; fullerenol; inflammation; tendinopathy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Characterization of fullerenol. (A) Transmission electron microscope (TEM) of fullerenol powder. Scale bar = 0.5 μm (left), 50 nm (right) (B) FTIR of fullerenol powder. (C) Image of aqueous fullerenol (50 mg/mL). (D) Hydrodynamic size of fullerenol in aqueous solution.
FIGURE 2
FIGURE 2
Biocompatibility of fullerenol with different concentrations. (A) Optical density (OD) value of TCs treated with different-concentration (0, 0.1, 0.3, 0.5, 1, 3, 5, 10 μg/mL) fullerenol at 1 and 3 days tested by CCK-8. (B) Live/dead cell staining of TCs treated with 0, 0.3, 1, 5 μg/mL fullerenol at 3 days. Scale bar = 25 μm. (Data are presented as the mean ± standard deviation. *p < 0.05, **p < 0.01).
FIGURE 3
FIGURE 3
Effects of fullerenol on inflammation of TCs induced by IL-1β. (A) mRNA level of COL1A1, TNC, MMP-3 and MMP-13 of TCs after fullerenol and IL-1β treatment tested by qRT-PCR. (B) Protein level of TNC, COL1A1 and MMP-13 of TCs after fullerenol and IL-1β treatment tested by Western Blot (Left) and quantitative results (Right). (C) ROS level of TCs after fullerenol and IL-1β treatment tested by ROS assay kit.
FIGURE 4
FIGURE 4
Migration of TCs after IL-1β (50 ng/mL) and fullerenol treatment. (A) Migration of TCs in control (Ctrl), IL-1β, IL-1β+0.3 μg/mL, IL-1β+1 μg/mL, IL-1β+5 μg/mL groups tested by scratch assay. Scale bar = 250 μm. (B) Migration of TCs in Ctrl, IL-1β, IL-1β+0.3 μg/mL, IL-1β+1 μg/mL, IL-1β+5 μg/mL groups tested by transwell assay. Scale bar = 100 μm. (C) Quantitative results of scratch assay. (D) Quantitative results of transwell assay. (Data are presented as the mean ± standard deviation. *p < 0.05, **p < 0.01).
FIGURE 5
FIGURE 5
Expression of MAPK signaling pathway after IL-1β (50 ng/mL) and fullerenol (0.3, 1, 5 μg/mL) treatment. (A) The phosphorylation levels of p38 in TCs of Ctrl, IL-1β, IL-1β +0.3 μg/mL, IL-1β+1 μg/mL, IL-1β+5 μg/mL groups were examined by Western Blotting. (B) Quantitative results of phosphorylation levels of p38. (C) The phosphorylation levels of Erk1/2 in TCs of Ctrl, IL-1β, IL-1β +0.3 μg/mL, IL-1β+1 μg/mL, IL-1β+5 μg/mL groups were examined by Western Blotting. (D) Quantitative results of phosphorylation levels of Erk1/2. (E) The phosphorylation levels of JNK in TCs of Ctrl, IL-1β, IL-1β +0.3 μg/mL, IL-1β+1 μg/mL, IL-1β+5 μg/mL groups were examined by Western Blotting. (F) Quantitative results of phosphorylation levels of JNK. (Data are presented as the mean ± standard deviation. *p < 0.05, **p < 0.01)
FIGURE 6
FIGURE 6
Inhibition of fullerenol (0.5, 1 mg/mL) on tendinopathy in vivo. (A) HE and Masson staining of tendons in Ctrl, Collagenase, Collagenase+0.5 mg/mL, Collagenase+1 mg/mL groups (Left). Statistical results of fiber alignment (Right). Scale bar = 50 μm. (B) Immunohistochemical staining (COL I, COX-2, IL-6) of tendons in Ctrl, Collagenase, Collagenase+0.5 mg/mL, Collagenase+1 mg/mL groups. Scale bar = 20 μm.
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References

    1. Adeoye A. O., Mukasheva F., Smatov S., Khumyrzakh B., Kadyr S., Shulgau Z., et al. (2022). A biomimetic synthetic nanofiber-based model for anterior cruciate ligament regeneration. Front. Bioeng. Biotechnol. 10, 969282. 10.3389/fbioe.2022.969282 - DOI - PMC - PubMed
    1. Aicale R., Bisaccia R. D., Oliviero A., Oliva F., Maffulli N. (2020). Current pharmacological approaches to the treatment of tendinopathy. Expert Opin. Pharmacother. 21, 1467–1477. 10.1080/14656566.2020.1763306 - DOI - PubMed
    1. Arnoczky S. P., Tian T., Lavagnino M., Gardner K. (2004). Ex vivo static tensile loading inhibits MMP-1 expression in rat tail tendon cells through a cytoskeletally based mechanotransduction mechanism. J. Orthop. Res. 22, 328–333. 10.1016/S0736-0266(03)00185-2 - DOI - PubMed
    1. Cai L., Mu Y. R., Liu M. M., Zhou M. Y., Meng B., Liu F. Y., et al. (2021). Penta-acetyl geniposide suppresses migration, invasion, and inflammation of TNF-α-stimulated rheumatoid arthritis fibroblast-like synoviocytes involving wnt/β-catenin signaling pathway. Inflammation 44, 2232–2245. 10.1007/s10753-021-01495-y - DOI - PubMed
    1. Cai L., Zhou M. Y., Hu S., Liu F. Y., Wang M. Q., Wang X. H., et al. (2022). Umbelliferone inhibits migration, invasion and inflammation of rheumatoid arthritis fibroblast-like synoviocytes and relieves adjuvant-induced arthritis in rats by blockade of wnt/β-catenin signaling pathway. Am. J. Chin. Med. 50, 1945–1962. 10.1142/S0192415X22500835 - DOI - PubMed