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Umbelliferone Ameliorates Complete Freund Adjuvant–Induced Arthritis via Reduction of NF-κB Signaling Pathway in Osteoclast Differentiation

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Abstract

Osteoclasts, bone-resorbing somatic cells, are directly responsible for bone destruction during rheumatoid arthritis. Complete Freund adjuvant (CFA) is a widely used animal model using rodents for studying rheumatoid arthritis (RA), which effectively manifests serious cartilage destruction and progressive bone erosion, affecting synovial joints and serious joint dysfunction. It was considered that joint injury in RA is induced through systemic inflammation pathway. Umbelliferone (UF), a coumarin derivative of Agele marmilosa, possesses anti-inflammatory activity. In the current study, we scrutinize the effect of umbelliferone on CFA-induced arthritis model and explore the possible mechanism on bone destruction. Intradermal administration of CFA (0.05 mL) was to induce RA manifestations in the experimental rats and the same oral administration of UF was received. The anti-arthritic activity of UF was determined by its inhibitory activity on various biochemical markers, viz., pro-inflammatory, inflammatory, antioxidant enzymes, and hematological parameters elevated during RA condition. We also estimated the mRNA expression of osteoclast parameters. Obtained result disclosed significant reduction in the paw edema and increment of the body weight after UF administration. UF reduce the inflammatory mediatory such as COX-2, PGE2, NF-kB, and VEGF; pro-inflammatory cytokines include TNF-α, IL-1β, IL-6, IL-10, and IL-17 significantly. Moreover, UF treatment significantly reduced the osteoclast number via modulating the RANKL/RANK/OPG ratio. Furthermore, administration of umbelliferone significantly (P < 0.001) suppressed the NF-κB and VEGF. Collectively, our results indicated the novel role of umbelliferone in osteoclastogenesis and proved that umbelliferone is a modern therapeutic tool as a natural agent for treating arthritis and other autoimmune disorders with bone degradation.

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Acknowledgments

The authors acknowledged the Department of Orthopedics Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, for guidance and support.

Funding

This study was self-funded.

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Authors and Affiliations

  1. Department of Articular Orthopaedics, The First People’s Hospital of Changzhou, Changzhou, 213000, Jiangsu, China

    Guofeng Wu

  2. Department of Orthopaedics, Shanxian Central Hospital, Heze, 274300, Shandong, China

    Wenbo Nie

  3. Department of Surgery, Hot Spring Sanatorium of Linyi, Shandong Coal (Linyi Hedong Central Hospital, Linyi, 276032, Shandong, China

    Qiu Wang

  4. Department of Rehabilitation, Shanghai Putuo People’s Hospital, Shanghai, 200060, China

    Youguo Hao

  5. Department of Spinal surgery, Baoshan Branch, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201999, China

    Shaohua Gong

  6. Department of Orthopedics, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, China

    Yuxin Zheng

  7. Department of Orthopedics Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China

    Hao Lv

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  1. Guofeng Wu
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Contributions

GW, WN, and QW designed the experimental study; YH, SG, and YZ estimation and interpretation the biochemical data. HL supervised all the experimental protocol and interpreted the data. All the authors equally contributed in manuscript editing. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Hao Lv.

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The whole experimental protocol was approved from the Institutional Animal Use and Care Committee and all institutional procedures and protocols (NIH guidelines) regarding the animal handling and care were followed.

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Wu, G., Nie, W., Wang, Q. et al. Umbelliferone Ameliorates Complete Freund Adjuvant–Induced Arthritis via Reduction of NF-κB Signaling Pathway in Osteoclast Differentiation. Inflammation 44, 1315–1329 (2021). https://doi.org/10.1007/s10753-021-01418-x

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