Tissue Eng Regen Med.
2019 Aug;16(4):335-343. 10.1007/s13770-018-0172-4.
Genome Engineering for Osteoarthritis: From Designer Cells to Disease-Modifying Drugs
- Affiliations
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- 1Department of Orthopaedic Surgery, Washington University in St. Louis, 1 Brookings Dr, St. Louis, MO 63130, USA. guilak@wustl.edu
- 2Shriners Hospitals for Children - St. Louis, 4400 Clayton Ave, St. Louis, MO 63110, USA.
- 3Department of Orthopaedic Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
- 4Center of Regenerative Medicine, Campus Box 8233, McKinley Research Bldg, Room 3121, St. Louis, MO 63110, USA.
- KMID: 2455043
- DOI: http://doi.org/10.1007/s13770-018-0172-4
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.
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