The authors in the review article titled "Rheumatic Disease: Protease-activated Receptor-2 in Synovial Joint Pathobiology" have written about the importance of protease-activated receptors (PARs) roles in inflammatory conditions of synovial joints. The review was very interesting and showed that future studies need to be done to investigate these receptors' crystal design to find their antagonists to target these receptors to decrease the inflammation in synovial joints of patients suffering from osteoarthritis rheumatoid arthritis.

Strengths:

1. The abstract gives the readers a good overview of the subject discussed in the article's body.

2. Since this is a review article, the authors used many papers to back up their points, which is excellent.

3. The authors used a figure representing the healthy joint compared to inflamed joints, and in this figure, they used titles right above each joint, making the readers' job easier. If someone wants to only look at the picture and not the caption, they can compare different synovial joint conditions by looking at the picture and title above it.

Comments:

1. The title is a very accurate representation of the paper. However, I'm not sure if the first part is essential since this receptor is activated in non-rheumatic diseases such as osteoarthritis.

2. The authors have not explained the DMARDs acronym that they used. I had to search for the abbreviation.

3. The authors could be more specific about the diseases they will mention in the text and the role of PAR2 in them. They mentioned that their study focuses on rheumatic diseases, but in reality, they only looked at two of those diseases, osteoarthritis and rheumatoid arthritis.

4. The authors have mentioned their take-home message. They did not mention the limitation of their review paper, but they have mentioned the research limitations on protease-activated receptors.

5. Between all of the authors, one author collaborates with many different companies and funding agencies. I would like to know if that had any effects on this papers' publication status. I got this information from the staff section of the University of Glasgow website that this author teaches.

6. It seems like one of the authors got the funding and then he and his collaborators publish papers about PAR2 even though only the focus of a few of those authors is PAR2 and the others are just usual collaborators of the author that got the funding. The other papers are:

• McCulloch, K., Huesa, C., Dunning, L., Litherland, G., Van ‘T Hof, R., Lockhart, J., & Goodyear, C. (2019). Accelerated post traumatic osteoarthritis in a dual injury murine model. Osteoarthritis And Cartilage, 27(12), 1800-1810. doi: 10.1016/j.joca.2019.05.027

• McCulloch, K., McGrath, S., Huesa, C., Dunning, L., Litherland, G., & Crilly, A. et al. (2018). Rheumatic Disease: Protease-Activated Receptor-2 in Synovial Joint Pathobiology. Frontiers In Endocrinology, 9. doi: 10.3389/fendo.2018.00257