Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP

Hiroko Habuchi; Masashi Izumi; Junpei Dan; Takahiro Ushida; Masahiko Ikeuchi; Kosei Takeuchi; Osami Habuchi

doi:10.1371/journal.pone.0252590

Peer Review History

Original SubmissionJanuary 19, 2021
9 Mar 2021 Decision Letter - Rosanna Di Paola, Editor PONE-D-21-01925 Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP PLOS ONE Dear Dr. Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by 5 days. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. 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Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Rosanna Di Paola, MD Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This is an interesting manuscript that addresses the role of mast cells in osteoarthritis pain in a chemically induced OA model. It has been shown before that mast cells may be involved in OA pathogenesis and pain but the detailed mechanisms are not known. The data shown in this manuscript may help us to understand the underlying mechanisms. The authors need to address the following questions. 1) The manuscript should be edited for clarity in English. 2) It seems that mast cells do not initiate joint pain but worsen joint pain in OA mice that suffer joint degeneration. In human, OA pain does not necessarily correlate with the extent of joint degeneration. The authors may want to quantify OA scores of the mice in different groups in Figure 3. This is to determine whether OA pain is related to joint degeneration in this OA mouse model. 3) The single limb standing may not be a well-established pain assessment method. Is there any literature about its efficacy in assessing OA pain? How does it compare to gait analysis or other more common pain assessment method? 4) The authors may want to add a mechanistic diagram to summarize their working hypothesis of the involvement of different joint tissues including fat pad, subchondral bone marrow, and synovium and the signaling pathways including PAR2, ATP, and inflammatory cytokines in inducing OA pain. Reviewer #2: Hiroko Habuchi and colleagues investigated about the role of mast cells in spontaneous pain induced by injection of sodium monoiodoacetate (MIA) into the knee joints of mice. The rational behind the study was clear and straight forward. The paper is clearly written, its original and of interest in its field, but some details are not clear. I recommend that the paper be accepted with minor revision: a) The authors should better emphasize the conclusions. b) The authors should clarify how they choose the number of mice used in their study. As to the methodology, please specify the number of animals used per each technique. c) While many different sources are used to set up the study in the introduction, little previous evidence is stated. Incorporating comparisons with other studies would increase the strength of the paper. Please refer to doi: 10.3390/ani10101827; 10.3390/antiox9060511; 10.1186/s13075-019-2048-y ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: Yes:** Qian Chen Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0252590.r001
Revision 1
14 Mar 2021 Author Response Dear Dr. Rosanna Di Paola Academic Editor PLOS ONE Thank you for your E-mail of March 9, 2021 about our manuscript entitled "Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP." (PONE-D-21-01925). I have amended our manuscript as far as possible in light of the opinion of the reviewers. To answer the question raised by the reviewer, we revised the manuscript. Answer to the reviewer For reviewer #1: 1) Some descriptions in Abstract (Line 26 and Line 33-36), Introduction (Line 55-57) and Discussion (Line 360, Line 366, Line 374 and Line 380) were modified for clarity in English. 2) In Fig 3, deterioration of superficial cartilage detected by toluidine blue staining was evident in mice belonging to A, B, E and F groups; however, significant difference in the degree of the deterioration was not observed among these groups. These results may be related to the clinical observation that OA pain does not necessarily correlate with the extent of joint degeneration. We added such description in Discussion (Line 398-402). 3) In the preliminary experiments, we have also observed stance score on the basis of the previously described methods (Heilborn U, Berge OG, Arborelius L, Brodin E. Spontaneous nociceptive behaviour in female mice with Freund's complete adjuvant- and carrageenan-induced monoarthritis. Brain Res. 2007 Apr 27;1143:143-9. doi: 10.1016/j.brainres.2007.01.054), and obtained basically the similar results to those from single paw standing; however, we adopted single paw standing for quantification of pain in this paper because single paw standing gave more quantitative data than stance score. 4) Our experiments clearly indicate that PAR2 and ATP are involved in the generation of spontaneous pain in OA; however, many other factors and different types of cells and tissues are possibly involved in elicitation of pain. We are concerned about too much simplification of the mechanistic aspect of OA pain by drawing a diagram that summarize our working hypothesis; therefore, we would like to omit the diagram that the reviewer has suggested. For reviewer #2: a) We described conclusion in the newly inserted section of Conclusion as follow: “Bone marrow derived mast cells (BMMCs) injected into the MIA-induced OA knee joints enhanced spontaneous pain, but these cells showed no pain-enhancing effects when injected into the knee joints of control mice that had not been treated with MIA. PAR2 and extracellular ATP were possibly involved in the pain-enhancing effects of BMMCs. “ (Line 430-434). b) We used enough mice to obtain significant results. Number of mice used for each experiment was described in the legends of Fig 4, Fig 6, Fig 7 and Fig 10. c) In introduction we added one paper about the effects of a pharmaceutical agent on the pain elicited in MIA-induced OA (Ref 28) (Line 70). We found after submission that Ref 49 was the same as Ref 27, so we deleted Ref 49. Accordingly Ref number was modified. We modified reference format to fit it to the PLOS ONE duideline. I believe that modification of the manuscript made this paper more correct and better. I would like to thank the reviewers for their kind comments. I hope this revised paper is now suitable for publication in the PLOS ONE. Sincerely yours, Osami Habuchi, Ph.D. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0252590.r002
19 May 2021 Decision Letter - Rosanna Di Paola, Editor Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP PONE-D-21-01925R1 Dear Dr. We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Rosanna Di Paola, MD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0252590.r003
Formally Accepted
24 May 2021 Acceptance Letter - Rosanna Di Paola, Editor PONE-D-21-01925R1 Bone marrow derived mast cells injected into the osteoarthritic knee joints of mice induced by sodium monoiodoacetate enhanced spontaneous pain through activation of PAR2 and action of extracellular ATP Dear Dr. Habuchi: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Rosanna Di Paola Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0252590.r004

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