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Treating osteoarthritis via gene therapy with rejuvenation factors

Gene Therapy volume 27, pages 309–311 (2020)Cite this article

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Cellular senescence and stem cell exhaustion are drivers of various aging-associated disorders, including osteoarthritis, a leading cause of disability and one of the most common degenerative diseases, the incidence of which increases with age [1,2,3,4]. Arthroplasty and autologous chondrocyte transplantation are osteoarthritis treatments, among which autologous chondrocyte transplantation is currently the most effective [5]. However, autologous chondrocyte transplantation is limited by the source of healthy donor cartilage and the proliferative capacity of primary chondrocytes [6]. More traditional treatment options involve mainly oral and intra-articular drugs and physical therapy (including electrotherapy and acupuncture). Nonsteroidal anti-inflammatory drugs, such as selective cyclooxygenase 2 inhibitors, are widely used due to their anti-inflammatory effects but may have adverse effects on the gastric mucosa and renal function and increase the risk for cardiovascular diseases. The analgesics used to ease patient pain are largely oral opioids and intra-articular corticosteroids. In addition, symptomatic slow-acting drugs, including glucosamine sulfate, chondroitin sulfate, and diacerein, are used. Furthermore, platelet-rich plasma seems to be another therapeutic option for the alleviation of osteoarthritis [7]. Despite the development of these therapeutic options, there is still no cure for osteoarthritis with nonsurgical disease-modifying treatment. Therefore, there is an urgent need for more specific therapeutic strategies developed on the basis of an in-depth molecular understanding of this disease.

Osteoarthritis usually emerges from disruption of the superficial zone of cartilage where mesenchymal stem cells (MSCs) and chondrocyte progenitor cells reside. Therefore, MSCs residing in the joint cartilage may be a critical target for the prevention of osteoarthritis [8]. Nonetheless, the key regulators of MSC senescence and aging-associated genes that act as potential targets for the treatment of human osteoarthritis are largely unknown. A comprehensive understanding of the underlying mechanisms of MSC senescence may help identify novel therapeutic targets for osteoarthritis.

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Fig. 1: Schematic of gene therapy using viral vectors encoding rejuvenation factors involved in the attenuation of osteoarthritis.

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Acknowledgements

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16010100), the National Key Research and Development Program of China (2018YFC2000100, 2018YFA0107203), the National Natural Science Foundation of China (81922027, 81870228, 81921006, 81625009, 91749202, 81861168034, 91949209), Program of Beijing Municipal Science and Technology Commission (Z191100001519005), Beijing Natural Science Foundation (Z190019), the State Key Laboratory of Stem Cell and Reproductive Biology and the State Key Laboratory of Membrane Biology.

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Authors and Affiliations

  1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China

    Jiahe Zhang, Guang-Hui Liu & Moshi Song

  2. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, 100101, Beijing, China

    Jiahe Zhang, Guang-Hui Liu, Jing Qu & Moshi Song

  3. University of Chinese Academy of Sciences, 100049, Beijing, China

    Jiahe Zhang, Guang-Hui Liu, Jing Qu & Moshi Song

  4. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, 100053, Beijing, China

    Guang-Hui Liu

  5. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China

    Jing Qu

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Zhang, J., Liu, GH., Qu, J. et al. Treating osteoarthritis via gene therapy with rejuvenation factors. Gene Ther 27, 309–311 (2020). https://doi.org/10.1038/s41434-020-0149-5

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