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Genome Engineering for Osteoarthritis: From Designer Cells to Disease-Modifying Drugs

  • Yun-Rak Choi
  • Kelsey H. Collins
  • Jin-Woo Lee
  • Ho-Jung Kang
  • Farshid Guilak
Review Article
Part of the following topical collections:
  1. Cartilage regeneration

Abstract

BACKGROUND:

Osteoarthritis (OA) is a highly prevalent degenerative joint disease involving joint cartilage and its surrounding tissues. OA is the leading cause of pain and disability worldwide. At present, there are no disease-modifying OA drugs, and the primary therapies include exercise and nonsteroidal anti-inflammatory drugs until total joint replacement at the end-stage of the disease.

METHODS:

In this review, we summarized the current state of knowledge in genetic and epigenetic associations and risk factors for OA and their potential diagnostic and therapeutic applications.

RESULTS:

Genome-wide association studies and analysis of epigenetic modifications (such as miRNA expression, DNA methylation and histone modifications) conducted across various populations support the notion that there is a genetic basis for certain subsets of OA pathogenesis.

CONCLUSION:

With recent advances in the development of genome editing technologies such as the CRISPR-Cas9 system, these genetic and epigenetic alternations in OA can be used as platforms from which potential biomarkers for the diagnosis, prognosis, drug response, and development of potential personalized therapeutic targets for OA can be approached. Furthermore, genome editing has allowed the development of “designer” cells, whereby the receptors, gene regulatory networks, or transgenes can be modified as a basis for new cell-based therapies.

Keywords

Genetics Gene editing Personalized medicine Osteoarthritis 

Notes

Acknowledgements

We acknowledge that this review is not exhaustive and the authors apologize to those whose work was not included due to space limitations. This study was supported in part by NIH Grants AR50245, AR48852, AG15768, AR48182, AG46927, OD10707, DK108742, EB018266, AR057235, AR073752, the Arthritis Foundation, and the Nancy Taylor Foundation for Chronic Diseases.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

There are no animal experiments carried out for this article.

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Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Orthopaedic SurgeryWashington University in St. LouisSt. LouisUSA
  2. 2.Shriners Hospitals for Children – St. LouisSt. LouisUSA
  3. 3.Department of Orthopaedic SurgeryYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Center of Regenerative MedicineSt. LouisUSA

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