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Osteoarthritic infrapatellar fat pad aggravates cartilage degradation via activation of p38MAPK and ERK1/2 pathways

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Abstract

Objective

This study aimed to investigate the biochemical effects of osteoarthritic infrapatellar fat pad (IPFP) on cartilage and the underlying mechanisms.

Methods

Human IPFP and articular cartilage were collected from end-stage osteoarthritis (OA) patients during total knee arthroplasty. IPFP-derived fat-conditioned medium (FCM) was used to stimulate human primary chondrocytes and cartilage explants. Functional effect of osteoarthritic IPFP was explored in human primary chondrocytes and articular cartilage in vitro and ex vivo. Activation of relative pathways and its effects on chondrocytes were assessed through immunoblotting and inhibition experiments, respectively. Neutralization test was performed to identify the main factors and their associated pathways responsible for the effects of IPFP.

Results

Osteoarthritic IPFP-derived FCM significantly induced extracellular matrix (ECM) degradation in both human primary chondrocytes and cartilage explants. Several pathways, such as NF-κB, mTORC1, p38MAPK, JNK, and ERK1/2 signaling, were significantly activated in human chondrocytes with osteoarthritic IPFP-derived FCM stimulation. Interestingly, inhibition of p38MAPK and ERK1/2 signaling pathway could alleviate the detrimental effects of FCM on chondrocytes, while inhibition of other signaling pathways had no similar results. In addition, IL-1β and TNF-α instead of IL-6 in osteoarthritic IPFP-derived FCM played key roles in cartilage degradation via activating p38MAPK rather than ERK1/2 signaling pathway.

Conclusion

Osteoarthritic IPFP induces the degradation and inflammation of cartilage via activation of p38MAPK and ERK1/2 pathways, in which IL-1β and TNF-α act as the key factors. Our study suggests that modulating the effects of IPFP on cartilage may be a promising strategy for knee OA intervention.

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Acknowledgements

We thank Prof. Lijun Lin for the help in sample collection. We also thank Wenquan Liang and Zhugui Chen for providing technical support. This work was supported by the National Natural Science Foundation of China (Grant No. 81773532, 81974342), China Postdoctoral Science Foundation (Grant No. 2021TQ0143), the Foundation of Hunan Educational Committee (Grant No. 20C1672), and Hunan Provincial Natural Science Foundation of China (Grant No. 2021JJ40518).

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Author notes

  1. Zuoqing Zhou and Su’an Tang have contributed equally to this work.

Authors and Affiliations

  1. Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

    Zuoqing Zhou, Su’an Tang, Xiaoyu Nie, Delong Li, Yang Zhao, Yumei Cao, Tianyu Chen, Guangfeng Ruan, Zhaohua Zhu, Weiyu Han & Changhai Ding

  2. Department of Orthopedics, The First Affiliated Hospital, Shaoyang University, Shaoyang, Hunan, China

    Zuoqing Zhou, Yiqun Zhang & Jianwen Yin

  3. Centre of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China

    Su’an Tang, Xiaoyu Nie, Delong Li, Yang Zhao & Weiyu Han

  4. Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China

    Tianyu Chen

  5. Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, Guangzhou, Guangdong, China

    Xiaochun Bai & Changhai Ding

  6. Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia

    Changhai Ding

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  1. Zuoqing Zhou
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Correspondence to Su’an Tang or Changhai Ding.

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Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of Zhujiang Hospital of Southern Medical University (Guangzhou, China). This work does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Communicated by Jason J. McDougall.

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Zhou, Z., Tang, S., Nie, X. et al. Osteoarthritic infrapatellar fat pad aggravates cartilage degradation via activation of p38MAPK and ERK1/2 pathways. Inflamm. Res. 70, 1129–1139 (2021). https://doi.org/10.1007/s00011-021-01503-9

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  • DOI: https://doi.org/10.1007/s00011-021-01503-9

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