Mast Cells Can Contribute to Joint Damage
New research shows that mast cells and the enzyme tryptase contribute to osteoarthritis.
The joint pain associated with aging is often caused by osteoarthritis. In contrast to rheumatoid arthritis, which is an autoimmune disease, osteoarthritis is thought to arise from the accumulated mechanical wear and tear of the joint that occurs through use or joint injury. The cartilage breaks down in the joint, which causes pain and difficulty moving. Researchers are trying to understand exactly how the immune system contributes to the joint damage rather than joint healing.
Research published in the journal eLife shows that mast cells are involved in the damage to cartilage that occurs with osteoarthritis. Mast cells are best known for their roles in allergies. Through a process called degranulation, activated mast cells release inflammatory mediators and enzymes, including the enzyme tryptase.
Wang and colleagues measured the amount of tryptase in the joint fluid of patients with osteoarthritis and patients with an injured joint but without osteoarthritis. The joints in each group of patients contained mast cells. The osteoarthritic joints had higher amounts of tryptase and degranulated mast cells, which are the ones releasing their inflammatory and tissue-degrading contents.
To show that mast cells were important for symptoms of arthritis, the researchers used two different genetically engineered mouse strains. Both of the engineered mice lacked functional mast cells, and both were protected from developing injury-induced osteoarthritis.
IgE is the antibody that activates mast cells. So, the researchers also tested whether mice engineered to lack IgE or the receptor that IgE binds were protected from osteoarthritis. Indeed, these mice were also protected, consistent with IgE-activated mast cells contributing to the development of persistent joint damage and osteoarthritis due to injury.
These findings with the genetically engineered mice suggested several strategies for therapeutic intervention. A drug that inhibited tryptase protected the mice from experimentally induced osteoarthritis. Blocking IgE from activating its receptor on the mast cells or inhibiting an enzyme needed for mast cell activation also spared joints from persistent damage resulting from injury.
Both the data from the patients and the studies with the mice indicate that activated mast cells contribute to the pathological tissue remodeling that occurs in joints and causes osteoarthritis. Future studies are needed to confirm in humans that the source of tryptase is mast cells and, if they are, that IgE is what stimulates these cells to degranulate. Despite these limitations, the findings from this study could be readily translated into clinical trials for treating and potentially preventing tissue damage and the development of osteoarthritis.
Q. Wang, C. M. Lepus, H. Raghu, L. L. Reber, M. M. Tsai, H. H. Wong, E. von Kaeppler, N. Lingampalli, M. S. Bloom, N. Hu, E. E. Elliott, F. Oliviero, L. Punzi, N. J. Giori, S. B. Goodman, C. R. Chu, J. Sokolove, Y. Fukuoka, L.B. Schwartz, S. J. Galli, W. H. Robinson, IgE-mediated mast cell activation promotes inflammation and cartilage destruction in osteoarthritis. eLife 8, e39905 (2019) DOI: 10.7554/eLife.39905.
Also of interest
N. R. Gough, Stem Cell Injections for Osteoarthritic Knees. BioSerendipity (8 January 2018). https://www.bioserendipity.com/2018/01/08/stem-cells-for-osteoarthritic-knees/
Cite as: N. R. Gough, Mast Cells Can Contribute to Joint Damage. Medium (14 August 2019).