The terms osteoarthritis and geriatric population are linked inherently. Osteoarthritis (OA) is defined as the irreversible degeneration of articular cartilage. It is the most common form of arthritis among older adults. According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, people with OA suffer from unbearable joint pain, mobility problems, improper gait balance, and difficulty executing activities of daily living., OA is common among those aged above 40 years.
The World Health Organization (WHO) has designated the period from 2021 to 2030 as the decade of healthy aging to highlight the requirement to address OA that strongly affects functional ability and quality of life. Recent research found that OA can further coexist with and, at the same time, negatively affect other chronic conditions. Thus, the OA hampers the overall quality of life of older adults and is a global health burden. Today, there is no cure for OA; only lifestyle modifications help in the management of the pain, as the National Institute of Arthritis and Musculoskeletal and Skin Diseases pointed out. However, a research paper recently published in Nature Communications has something different to share.
New evidence of OA trigger
The collaborative research conducted by scientists from the University of Adelaide, Australia, and Columbia University, USA, showed promising results in the effective management of OA with the help of stem cells. Stem cells are pluripotent, progenitor cells that are capable of proliferating into any cell line. The new study indicates the importance of stem cells in OA management after conducting an experiment with mouse models to identify the BMP-antagonist Gremlin 1 (Germ1) gene. It is a bi-potent chondrogenic and osteogenic progenitor cell present in the articular surface of the joints. Joint injuries induced by OA and other medical conditions associated with senescence deplete these progenitor cells. In the mouse model, it was found that ablation of Grem1 cells also leads to the development of OA.
Researchers did a functional and transcriptomic analysis in the mouse model and found that Grem1 lineage cells in the articular surface are dependent on Foxo 1, and ablation of Foxo1 in Grem1- lineage cells is caused by OA.
The authors indicated that Fibroblast Growth Factor (FGF) 18 [clinically known as Sprifermin], when transfused, acts as a pathway activator to induce the proliferation of the Grem1- lineage chondrocyte progenitor cells, increasing cartilage thickness and reducing the severity of pain of OA. The experiment was conducted over the mouse model for 5 years in order to establish statistically significant results for the management of incurable OA.
The findings help in redefining OA as a pharmaceutically reversible loss of articular cartilage stem cells rather than an irreversible loss of cartilage tissues. In an interview, Ng, one of the authors of the paper, from the University of Adelaide, said that the study will allow further research to explore pharmaceutical options for targeting the stem cell lineage that is responsible for the formation of the articular cartilage, restricting the exponential progression of osteoporosis Though this discovery is limited to animal models, there are genomic similarities between mice and human samples. Moreover, the human trials are also ongoing.
References
Johnny von Einem. (2023). New hope to treat and reverse osteoarthritis. University of Adelaide. https://www.adelaide.edu.au/newsroom/news/list/2023/10/31/new-hope-to-treat-and-reverse-osteoarthritis
National Institute of Arthritis and Musculoskeletal and Skin Diseases. (2023). Osteoarthritis. https://www.niams.nih.gov/health-topics/osteoarthritis#:~:text=Osteoarthritis%20is%20a%20degenerative%20joint,a%20short%20period%20of%20time.
Ng, J. Q., Jafarov, T. H., Little, C. B., Wang, T., Ali, A. M., Ma, Y., … & Mukherjee, S. (2023). Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis. Nature Communications, 14(1), 6909. DOI https://doi.org/10.1038/s41467-023-42199-1
Steinmetz, J. D., Culbreth, G. T., Haile, L. M., Rafferty, Q., Lo, J., Fukutaki, K. G., … & Singh, S. (2023). Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet Rheumatology, 5(9), e508-e522. DOI: https://doi.org/10.1016/S2665-9913(23)00163-7
Zakrzewski, W., Dobrzyński, M., Szymonowicz, M., & Rybak, Z. (2019). Stem cells: past, present, and future. Stem cell research & therapy, 10(1), 1-22. DOI https://doi.org/10.1186/s13287-019-1165-5
